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The 

Hypodermic 

Syringe 



BY 



GEORGE L. SERVOSS, M. D. 

M 

Editor of "Nevada Medicine" 

Member of the Nevada State Medical Association 

Fellow of the American Medical Association 



PHYSICIANS DRUG NEWS CO. 

PUBLISHERS 

Newark. New Jersey, IT. S. A. 






.S4 



COPYRIGHT MM 

n 

GEORGE L BEBVOB8, M. D. 



APR 30 1914 



^V 






)a.A371652 






JBetricatton. 



TO THE MAN VI HO TAUGHT ME THE 
SECRETS OF HYPODERMIC MEDICATION 

JOHN H. OLIVER, M. D. 

IS THIS BOCK AFFECTIONATELY 
DEDICATED. 



CONTENTS. 



CHAPTER I Pase 

Introduction l 

CHAPTER II 
The Syringe II 

CHAPTER III 
Technique . 21 

CHAPTBB IV 

Remedies 29 

EAPTER V 

Drugrs and 

CHAPTBB vi 

Drutrs ir Continued 47 

VII 
Mercurials 53 

CHAPTER VIII 
Antitoxin 'Turns . 63 

CHAPTER IX 

Bacterins 

CH x 

Bacterins — Contiir 117 

CHAPTER M 

Bacterins — Continued 

CHAPTER XII 

Bacterins — Continued ... 

\III 
Bacterins — Continued . . 

CH.\ XIV 

Tuberculins 

CHAPTER XV 

Anesthesia 

CHAPTER XVI 
Shock . 303 

CHAPTER XVII 
Syphilis 313 



PREFACE. 

It is now several years since Bartholow offered us 
his little work on Hypodermic Medication. This book 
has long been out of print and now is seemingly, after 
various attempts on our part to secure a copy, is out of 
the market as well. In the following pages it has not 
been the attempt of the author to inject anything of an 
original nature, but rather to give a condensed narrative 
of the hypodermic syringe and its possibilities, as set forth 
by numerous authors and investigators. It is very proba- 
ble, in view of the wonderful strides made in hypodermic 
medication in recent years, that many omissions will be 
found. Without other apologies, we offer this little 
book. 

George L. Servoss, M. D. 



CHAPTER I. 

Introduction. 

Less than a century ago the hypodermic syr- 
inge and the hypodermic method of medication 
were first brought into use. Primarily, those 
who used the instrument, employed it for the 
quick introduction of morphine for the relief 
of pain and it became a common comment that 
he who used the instrument, did so for the pur- 
pose of administering this drug and no other. 
This idea lingers in the minds of many, even 
today. 

However, with the passing of time, it was 
found that many other drugs might be exhib- 
ited in this way, and the hypodermic method 
paved the way for a greater and better drug 
application. Not only have been drug agents 
employed by this method, but it opened an 
avenue for the application of many substances 
which could not be administered orally, be- 
cause of the destructive action of the digestive 
ferments of the alimentary canal. 

Not only did this method allow of the rapid 
introduction of a drug into the system, but it 
was found, as time went on, that smaller doses 
were effective when administered in this man- 



8 THE HYPODERMIC SYEINGE. 

ner, because of the fact that all of the drug 
was absorbed, which was not always the case 
when drugs were exhibited by the mouth. 

Many drugs, administered orally, brought 
about that condition know as idiosyncrasy, 
which was found not to be the case when the 
same were given hypodermically, and because 
of this fact it is very probable that many lives 
were saved through the use of the instrument. 

Many drugs, such as iron which was invari- 
ably followed by constipation, when given by 
the mouth, gave undesirable results, were 
found to produce nothing of this sort when the 
hypodermic method was employed in their in- 
troduction. This fact undoubtedly has had 
more to do with the numerous advances in 
drug improvement than any other one thing, 
as the pharmacists and chemists have been 
working toward the end where it will be pos- 
sible to administer every known drug, in one 
form or another, through the use of the hypo- 
dermic syringe. 

To employ any drug agent by the hypo- 
dermic method, it must be pure, clean and 
readily absorbed, and for this reason, in order 
that drugs may be employed in this manner, 
the hypodermic syringe has been the means to 
the end whereby active agents have become the 
rule and not the exception. In the beginning 
there were but few drugs which could be em- 
ployed in this manner ; a few of the alkaloids, 
and even these, in the earlier days were far 
from pure. Recognizing the fact that only the 



THE HYPODEEMIC SYKINGE. 9 

active principles of drugs could be employed 
by the hypodermic method, efforts were made 
to segregate and isolate such principles in their 
purest possible form, until today we find that 
the list of agents applicable in this manner are 
becoming legion. Many of the chemicals, 
which in their simple forms could not be so 
employed, have within recent years been offer- 
ed in organic form and non-irritable, and today 
we see iron, arsenic and the mercurials in such 
form being employed to a very considerable ex- 
tent by this method. 

Primarily the hypodermic syringe was used 
to introduce remedial agents only beneath the 
skin, but as time went on it was found that, in 
many instances better action was obtained if 
the injections were thrown deeper into the 
muscular tissues, and still later the intravenous 
mode was adopted and the agent thrown di- 
rectly into the blood-current. Still later the 
method of throwing drugs and other sub- 
stances directly into the spinal cavity was in- 
troduced, and in some instances the instrument 
has been employed to throw therapeutic agents 
directly into the cerebral cavities, and into the 
cerebral meningeal cavities. 

Some three decades ago cocaine was intro- 
duced and it was found that it was a local ob- 
tundant when applied to surfaces where ab- 
sorption was possible. The hypodermic syringe 
allowed of its use in the obtunding of skin and 
deeper tissues, through the throwing of solu- 
tions of the drug beneath the surfaces by 



10 THE HYPODERMIC SYRINGE. 

means of the syringe. Thus was born local 
anesthesia and it was made possible through 
the hypodermic method, which would not have 
been possible otherwise. It also made possible 
spinal anesthesia, which followed shortly after 
that of a local nature. 

While it is true, and more's the pity, that 
the hypodermic syringe has been blamable for 
the production of the drug habit in many, 
nevertheless, the fact that it has saved mam 
more lives than it has cursed, makes the instru- 
ment one of the most valuable in the hands of 
the medical profession. 

It is not, however, an instrument to be em- 
ployed indiscriminately, and more especially 
when narcotic drugs are employed by this 
method. The person who employs it in s 
manner is guilty of a crime against humanity 
and, as a rule, is not a successful practitioner. 
It is an instrument only for emergencies, in 
the introduction of narcotics, and never should 
be employed otherwise than as such. The contin- 
ued use of the narcotics is rarely indicated, and 
when such indications are met, drugs of this 
character are better administered orally, in 
that the patient may not become aware of the 
fact that habit forming drugs are being admin- 
istered, as the moral effect of the agent may 
be greater than is the physical. 

As has been said, the hypodermic method has 
paved the way toward a greater and better 
materia medica. Had it not been for the in- 
vention and introduction of the hypodermic 



THE HYPODERMIC SYRINGE. 11 

syringe it is very probable that many of our 
biological products, such as the antitoxins, bac- 
terins or bacterial vaccines and substances of 
this character would never have been brought 
forth, as it is a known fact that many of these 
substances become inactive when exhibited by 
way of the alimentary canal, but are highly 
active when introduced subcutaneously, intra- 
venously or thrown into the spinal cavity. In 
this way not only has the hypodermic syringe 
shortened disease, but in addition has lowered 
mortality to an astonishing extent. 

The hypodermic has simplified anesthesia 
through the allowing of the introduction of ob- 
tunding drugs, both locally and generally and 
to such an extent that operative and post-oper- 
ative shock have been practically obliterated. 
Local anesthesia has done away with the neces- 
sity of general anesthesia in many minor sur- 
gical operative procedures, and had it not been 
for the hypodermic syringe this could not have 
been possible. 

Many diseases, considered incurable under 
the older methods of drug administration, are 
now showing either improvement or satisfactory 
termination when the hypodermic method is be- 
ing employed. Because of this, and for various 
other reasons, the hypodermic method of drug 
administration has become a boon to humanity. 



CHAPTER n. 

The Syringe. 

The instrument most commonly employed is 
a simple plunger pump consisting of a barrel, 
piston, rod, finger and thumb pieces and 
needle. Primarily a hard rubber syringe was 
employed to which a needle was attached. 
Later, an instrument with a glass barrel, with 
leather plunger was introduced. The objec- 
tions to both the rubber and initial glass syr- 
inges, were that both were equipped with 
leather washers, which frequently, unless the 
instrument was used continuously, or given 
frequent attention, dried out, and at the mo- 
ment when the syringe was most needed, it 
was found inactive as a pump, simply because 
of the fact that the looseness of the plunger 
and its lack of contact with the barrel allowed 
of no suction or propelling force. Endeavors 
to overcome this objection were made. In one 
instrument the piston rod was made hollow and 
filled with oil which was fed automatically to 
the plunger, thus keeping the latter soft and 
expanded, but this instrument had its objec- 
tion in that too much of the lubricant was pres- 
ent at all times and that it was kept clean with 



14 THE HYPODERMIC SYRINGE. 

difficulty. In another instrument the piston 
rod was continued beyond the plunger and a 
nut applied below the second washer of the 
plunger, this nut being supplied with nibs or 
projections which fitted into corresponding de- 
pressions in the lower end of the barrel, thus 
allowing of tightening with a few turns of the 
rod, and acting to expand the washers through 
mechanical force. This instrument was supe- 
rior to others of the leather washer type, but, 
unless the washers were kept moist, the me- 
chanical force became ineffective beCJ 
the fact that pressure had n dry 

washers. Another objection to the leather 
washers was the fact that they were liable to 
disintegration and that particles of leather 
were carried into the needle to clog that por- 
tion of the instrument, or were thrown into the 
tissues to become possible irritants, <>r worse 
if the instrument were employed to introduce 
drugs intravenously, to act as foreign bodies 
in the circulation. 

Later on asbestos, either in the shape of 
sheet washers, or cord wound about the piston, 
was substituted for leather, but it was found 
objectionable for many of the same reasons as 
was the leather plunger. It dried out and dis- 
integrated. It had one superiority over leath- 
er; it could be kept clean with greater ease. 
Rubber was used as plunger and washer ma- 
terial, but with but little success, as any greasy 
lubricant caused rapid disintegration, and if 
the syringe were not lubricated it was operated 



THE HYPODERMIC SYRINGE. 15 

with difficulty, because of the tendency of the 
soft rubber to cling tightly to the barrel walls. 
Recognizing the fact that a radical change 
must be made in the syringe, if it were to be 
invariably useful and effective, and under all 
conditions, the instrument makers introduced 
the all metal hypodermic. In this both barrel 
and plunger are of solid metal, the one being 
ground to accurately fit the other, thus giving 
a perfect contact and likewise perfect suction 
and propelling force. One objection to this in- 
strument is the fact that, being supplied with 
a solid metal barrel, the operator cannot see 
just what he is doing, and if employing the 
instrument for the introduction of agents em- 
ployed for the establishment of local anes- 
thesia, is obliged to rely wholly upon the scale 
upon the piston rod in order to determine just 
how much of the solution is being introduced. 
This, however, is not a serious objection. An- 
other objection lies in the fact that this instru- 
ment must be perfectly lubricated in order to 
have it perfectly effective in propelling and 
suction force, but this objection is overcome if 
aseptic greases, as petrolatum, are employed, 
but even then there is no absolute certainty 
that the instrument is aseptic at all times, as 
the upper portion thereof is not absolutely 
tight. However, this type of syringe may be 
rendered clean through boiling or the applica- 
tion of antiseptics. Care should be taken not 
to employ sublimate solutions for this purpose, 
excepting in emergencies, as the continued use 



16 THE HYPODERMIC SYRINGE. 

of this agent would eventually corrode 
both barrel and plunger, thus rendering the 
instrument imperfect through lack of contact 
between these portions. This type is, however, 
one of the most satisfactory we possess, as it 
overcomes the major portion of the objections 
offered to those before mentioned. 

To overcome the objections to the all metal 
syringe, the glass barrel instrument, with solid 
steel plunger was introduced. In this instru- 
ment, instead of coming in direct contact with 
the barrel, the plunger was fitted tightly into 
a cork washer at the top of the barrel, and ex- 
erted suction and propulsion through air dis- 
placement. If the washer fitted the plunger 
snugly this instrument acted admirably, but if 
there were any deviation of contact it became 
worthless, as a vacuum was an impossibility. 
However, in point of cleanliness, this instru- 
ment was a distinct improvement over the 
others heretofore mentioned. 

The Koch type, in which a soft rubber bulb 
at the top of the instrument produced suction 
and propulsion, had some superior points, but 
owing to the liability of disintegration of the 
bulb, with the necessity of frequent renewals, 
and also the fact that lack of contact between 
the bulb and barrel might occur, this type has 
not become greatly popular. It has, however, 
some advantage over the piston types. No 
lubrication is required and it is easily kept 
clean. 



THE HYPODEBMIC SYSINGE. 17 

Following closely upon the trail of the glass 
and metal types.appeared the all glass, or Luhr 
type, in which a solid glass plunger is accurate- 
ly ground into the barrel, thus affording a 
perfect contact. This instrument has the ad- 
vantage that lubricants are unnecessary, as the 
fluids employed allow of free action. This 
instrument may be kept absolutely clean, 
either by boiling or by treatment with any of 
the chemical antiseptics. In emergencies, when 
boiling is impossible, it may be rendered aseptic 
through the application of alcohol, phenol or 
immersion in sublimate solution, and this with- 
out the least fear of damage to the instrument. 
The only objection to the Luhr type is its 
friability and liability to breakage, and the 
fact that after use, especially with any of the 
salts, it must be thoroughly washed out, else 
these crystallize and cause the plunger to ad- 
here to the inner sides of the barrel. Should 
this occur, boiling of the instrument becomes 
necessary. This fact should be remembered, lest 
the syringe be out of commission when needed 
in an emergency, and when time for cleaning 
might not be allowable. 

Another type which is in use is that in which 
a metal plunger is employed with a glass 
barrel, the former being ground to accurately 
fit the latter. The main objection to this type 
is that it must be boiled to be rendered aseptic. 
It has the superiority over the all-metal 
syringe, in that the operator may see the con- 
tents of the barrel. This instrument is used 



18 THE HYPODERMIC SYRINGE. 

in instances when more than ordinary force 
is desired, as in the introduction of large quan- 
tities of fluids into the deeper muscular tissues, 
or where the obtunding effects of pressure are 
desirable. 

In the original syringes there were numerous 
packing washers, usually of leather, and these, 
unless the instrument was kept in good con- 
dition, were liable to dry out and allow of 
leakage at either or both ends of the barrel, 
with consequent lack of proper suction and 
propulsion. Not infrequently did the opera- 
tor find his instrument worthless after a long 
period of non-use, simply because of this dry- 
ing out and shrinkage of the packing. The 
needle, in the earlier types, was threaded to 
a nipple at the lower end of the barrel, with 
an interposing washer to prevent leakage, and 
this, like all other washers had a tendency to 
dry out, and that very rapidly, thus allowing 
that which it was supposed to prevent, serious 
leakage. 

With the introduction of the all metal type 
all of the washers employed as packing, with 
the exception of the one between the needle 
and barrel, were obliterated, although in some 
instances this objection was overcome by 
fitting the needle to the nipple by means of a 
slip, or friction, joint. In the all-orlass 
barreled type the washers are practically all 
done away with, as they are unnecessary. The 
needle in these syringes is ground to accurately 
fit a ground nipple, the contact by cohesion 



THE HYPODERMIC SYKINGE. 19 

allowing of a practically tight joint, which 
under ordinary circumstances, does not leak. 

Recently there has been introduced a new 
type. This consists of a collapsible, block-tin 
tube containing the drug in solution and ready 
for application, and to which the needle is 
permanently attached, the instrument being 
sealed by means of a wire passed through 
the needle. The latter is covered by a 
glass capsule, and being originally aseptic 
remains in such condition until used. Aside 
from additional expense, this type is ideal, 
in that cleanliness is practically assured and 
because of the fact that the instrument is used 
but once and then thrown away, overcoming 
any possible tendency to carry infection from 
one patient to another through carelessness. 

Hypodermoclysis, or the throwing of large 
quantities of fluids into the subcutaneous tis- 
sues, is one of the outcomes of the hypodermic 
method. This operation, which requires slow- 
ness in introduction is carried out through the 
use of gravity, rather than syringe propulsion, 
the douche bag or can being the instrument 
employed, and the force graduated by the fall 
of the fluid. Gravity is also employed in the 
introduction of fluids into the spinal cavity. 



CHAPTER III. 

Technique. 

Preparation of the Syringe — If the glass 
barreled syringe, either with leather, asbestos 
or rubber plunger is employed, it should be 
boiled and care should be taken to see that 
no bits of the plunger are in the solution used. 
If there is not time to thoroughly boil the in- 
strument it may be rinsed, inside and out, with 
either 95 per cent, alcohol, or a solution of 
one of the chemical antiseptics, but it should 
be borne in mind that a corrosive sublimate 
solution may work havoc, through its attack 
upon the metal parts. 

The all-metal type may be cleaned by boil- 
ing, or by the use of alcohol or chemical anti- 
septics, but care should be taken not to use 
bichloride, for fear of corrosion, which will, 
in time, interfere with the suction force. 

The above remarks apply, in the main, to 
those instruments having glass barrels with 
metal plungers. 

The all-glass type offers none of the objec- 
tions or obstacles presented by those hereto- 
fore mentioned. Instruments of this type may 
be boiled, treated with alcohol, or immersed 



22 THE HYPODERMIC STRINGS. 

in any of the solutions of chemical antiseptics, 
without fear of interference with the working 
of the instrument. 

In any event, no matter what type of syringe 
is employed, it should invariably be rinsed 
thoroughly with sterile water prior to drawing 
up the drug carrying solution, as many of the 
antiseptic agents may prove irritant and cause 
more or less subsequent trouble. 

In doing a hypodermoclysis, the fountain 
syringe, or tank, should be rendered thorough- 
ly aseptic, in one way or another. The rubber 
bag and tubing may be boiled a few times with- 
out danger, but frequent boiling may e 
disintegration of the material. The pouring 
of a hot solution of one of the chemical dis- 
infectants through the bag and tube will 
usually suffice. With the metal or glass tank, 
boiling will render the receptacle aseptic, and 
as there is usually plenty of time for this pro- 
cedure, it should be carried out in every in- 
stance. 

Preparation of the Needle — It goes without 
saying that it is as important, if not more so, 
to have the needle as aseptic as is the body of 
the syringe. If a needle is properly cared for 
after each injection, and as is frequently the 
case, kept in alcohol when not in use, there 
need be but little fear of trouble or infection 
from a dirty needle. However, prior to use, 
and after attachment to the body of the sy- 
ringe, the needle should be subjected to fur- 
ther attention. Immersion in 95 per cent, al- 



THE HYPODEEMIC SYRINGE. 23 

cohol usually assures cleanliness, but in full 
strength tincture of iodin gives greater as- 
surance that infection will not follow the wake 
of the use of the instrument. After receiving 
this treatment the needle should not be 
touched, in fact this latter treatment should 
be given just prior to its being plunged under- 
neath the skin. In making deep puncture into 
the muscle many find that a needle dripping 
with iodin is never followed by abscess, or even 
irritation. After the application has been 
made, full strength alcohol should be drawn 
into the syringe and thrown out, and this re- 
peated two or three times. If this is done the 
instrument will be prefectly cleaned and will 
also dry wholly and quickly. If this plan is 
followed it will not be necessary to keep a 
wire within the needle during the intervals of 
non-use, as its lumen will remain open. 

Preparation of the Skin — As in all opera- 
tions where the epidermis is to be broken, even 
though the puncture from the hypodermic 
needle is very slight, absolute cleanliness must 
be observed. When the smaller needles are 
used and but one application is to be made it 
may not be necessary to scrub the area, but 
some antiseptic should be applied. Some swab 
the surface with a 95 per cent, alcohol, with 
ether, or a solution of some chemical antiseptic. 
Today, with the recognition of the value of 
tincture of iodin in skin disinfection, it is 
probable that this agent gives us the best 
means whereby to guard against local infec- 



24 THE HYPODERMIC SYRINGE. 

tion, incident to the use of the hypodermic. 
In the use of this agent the site of puncture 
is painted over with a sufficiently strong solu- 
tion of iodin in alcohol to warrant asepsis. 
When the skin is treated in this manner and 
a clean syringe and needle are used, there is 
but little chance of abscess formation. If a 
needle of large caliber is to be used, as is 
hypodermoclysis, it will be well to scrub the 
skin, as for a surgical operation, prior to the 
application of the iodin solution. 

Methods of Hypodermic Administrations — 
It goes without saying that all agents em- 
ployed hypodermically must be in per 
solution, and in such condition as to be readily 
and rapidly absorbed, and that there must not 
be any foreign or solid matter present. The 
solution must also be sterile, else infection fol- 
low. Nor should, if it can be helped, the liquid 
injected be irritant. 

When a single injection, of small quantity, 
is to be made, any portion of the skin surface 
may be selected as the site of operation. It 
was the habit at one time to pick up a fold 
of the skin between the thumb and forefinger 
of the left hand and to plunge the needle into 
the skin so picked up and some still follow this 
plan. This is not, however, a good procedure, 
as there is more or less liability of bruising 
of the tissues so picked up, with a possibility 
of resultant abscess. The needle may be easily 
introduced into the subcutaneous tissues with- 
out picking up the skin. Another method is 



THE HYPODERMIC SYRINGE. 25 

to plunge the needle deeply into the underly- 
ing muscular tissues. It is very probable that 
absorption takes place with greater rapidity 
from the subcutaneous than from the mus- 
cular tissues, although from either method 
good results have obtained. Where slower ab- 
sorption is desired, as in the administration 
of salvarsan, the intramuscular method is un- 
doubtedly preferable. The skin of the fore- 
arm is usually the site of the single injection. 

When several injections are to be made, as 
in the administration of iron cacodylate, and 
other agents of this character, the preferable 
site is in the tissues below and to the right 
of the left scapula. There is an abundance of 
cellular tissue at this point and the skin and 
surrounding tissues not being highly organized 
and sensitive, but little, if any, discomfort is 
experienced by the patient, even though num- 
erous injections may be given. Absorption 
takes places readily from this particular site, 
and this should be remembered when the 
bacterins and antitoxins are to be administered. 

In performing a hypodermoclysis the needle 
should be of large caliber and introduced at 
a point where there is considerable cellular 
tissue, as large amounts of fluids are usually 
employed and must be thrown where they may 
have the greatest room and at the same time be 
absorbed rapidly. The abdominal and chest 
walls are the usual sites selected, although a 
good location is beneath the left scapula. 



26 THE HYPODEKMH SYRINGE. 

When using the hypodermic for intravenous 
injections scrupulous cleanliness must be ob- 
served at every step. One of the veins of the 
arm is usually the accepted site. The skin 
should be prepared as for surgical operation 
and the instrument rendered thoroughly 
aseptic. The operator, as regards his own per- 
son, should be as careful as in a major surgical 
operation. Care should be taken to see that 
the solution employed is perfect, sterile, and 
carries no solids, absolutely. The vein is ren- 
dered prominent by tourniquet, not sufficiently 
tight to totally obliterate the circulation com- 
pletely and the vein is either cut down upon 
and exposed, or the needle is plunged through 
skin, subdermal tissues and vein wall. The 
latter method is preferable, if possible, and it 
usually is. After the injection the resulting 
puncture is covered with a drop of collodion, 
or painted with tincture of iodin. If an incision 
has been required the resulting w T ound is 
treated as is any other surgical incision. The 
treatment of the puncture is usually necessary 
in intravenous injections because of the fact 
that a needle of considerable caliber is usually 
employed. 

In making the puncture, either subdermally 
or intramuscularly, the needle should be in- 
troduced with a quick thrust, and withdrawn 
slowly, introducing the fluid as withdrawal 
is being made. In this way the fluid is dis- 
tributed over a larger area and gives less dis- 
comfort to the patient, besides offering greater 



THE HYPODERMIC SYRINGE. 27 

ease of absorption. Either in the subcutaneous 
or intramuscular method the needle should be 
plunged to its full length before any of the 
fluid is thrown from the syringe. 

In making injections into the spinal cavity 
a measured amount of the spinal fluid should 
be withdrawn and a like amount of the solu- 
tion used injected. It goes without saying 
that spinal injection should be made with the 
greatest efforts toward asepsis. 

The antitoxins, bacterins, tuberculins and 
other biologic products should be injected at 
such points as favor the greatest rapidity of 
absorption. The methods in this connection 
will be considered at greater length in those 
pages in which the biologic products will re- 
ceive especial attention. 



CHAPTER IV. 

Remedies. 

During the earlier days of hypodermic med- 
ication it was suspected that morphine was to 
be employed with every production of the sy- 
ringe, and to a certain extent this idea pre- 
vails today in a vast majority of instances. 
This is not, however, the truth at this time, as 
the number of other agents so exhibited might 
be said to be legion. In fact it might be said 
that the practice of medicine could be carried 
on successfully without administering more 
than a few drugs, or other agents, orally. 

Not only are the chemical drugs and the 
alkaloids of plants so employed, but some of 
the whole plant products as well. We find the 
eclecties injecting considerable quantities of 
fluid lobelia hypodermically, and ergot, in 
aqueous extract, has been so employed. 

With the discovery of diphtheria antitoxin 
the value of the hypodermic syringe was in- 
creased manyfold, as it paved the way for the 
introduction of numerous other biologic 
products. Not only has the hypodermic be- 
come an absolute necessity in the exhibition 
of the biologic products, but likewise in the 



30 THE HYPODERMIC SYRINGE. 

administration of many drugs either wholly 
or partially inactive when introduced via the 
alimentary canal. 

The method allows of the application of the 
majority of the alkaloids, as well as many of 
the other active principles and concentrations 
of plant drugs, and not only does it assure of 
prompt reaction, but in addition practically 
gives an absolute assurance of full drug effect 
in every instance, as none of the agent is lost 
through lack of absorption, as is so frequently 
the case following oral exhibition. 

In the earlier days of hypodermic medication 
stock solutions of the drugs employed were 
kept on hand. While they may have I 
active when freshly prepared, they like all 
fluid mixtures were liable of deterioration, and 
to become foul. Abscesses occurred to a 
greater or less extent when such solutions 
were used, and it was due undoubtedly to a 
large extent, to their unclean condition. With 
the establishment of the manufacturing 
pharmacist and the introduction of tablet 
triturates, those drugs to be employed hypo- 
dermically were offered in such form, each 
tablet carrying the average dose of the drug 
to be employed. This not only gave a greater 
assurance of cleanliness, but an absolute as- 
surance of uniform dosage. In the beginning 
only a few of the alkaloids, such as morphine, 
strychnine, atropine, etc., were made, but with 
the recognition that many other agents were 
applicable in this manner the list grew to one 



THE HYPODEKMIC SYEINGE. 31 

of large dimensions, and is still receiving ad- 
ditions so rapidly that one is obliged to give 
the matter daily study to be down-to-date. 

Among the drug and chemical agents em- 
ployed and listed at present we find the fol- 
lowing in tablet form, either alone or in com- 
binations : 

Aconitine 

Apomorphine 

Aspidospermine 

Atropine 

Cactin 

Caffeine 

Cocaine 

Codeine 

Colchicine 

Condurangin 

Digitalin 

Ergotin 

Eucaine 

Gelseminine 

Heroin 

Corrosive Sublimate 

Hyoscine 

Hyoscyamine 

Mercury Succimide 

Morphine 

Nitroglycerine 

Xuclein 

Physostigmine 

Pilocarpine 

Picrotoxin 



32 THE HYPODERMIC SYRINGE. 

Quinine and Urea Hydrochloride 

Scopolamine 

Sparteine 

Strychnine 

Numerous combinations are offered in which 
the above list of drugs figure, but it is not 
necessary to mention them in these pages. Nor 
is it necessary to give the list of hypodermic 
solutions, as these are employed but seldom, 
usually in institutions, if at all, and rarely 
there. 

Many chemicals and other drugs are now 
offered in sterile solution in hermetically 
sealed ampules, especially the cacodylatea of 
iron and sodium, as well as of mercury, sev- 
eral of the mercurials, camphorated oil, ergot, 
strophanthin and many other products, a list 
too long to be given space in these pages, and 
one which is still far from being complete, as 
additions are being made daily thereto. The 
ampules, like the tablet triturates, represent 
the average adult dose. Among the advan- 
tages of the ampule are that the contents is 
prepared and ready for use, a uniform amount 
of the drug is offered and that the solution 
is clean and sterile. 

In the treatment of specific infectious dis- 
eases the following antitoxins and serums are 
employed, and are offered in specified units 
of dosage in aseptic syringes, as a rule: 



THE HYPODERMIC SYRINGE. 33 

Diphtheria Antitoxin 
Tetanus Antitoxin 
Anti-Dysenteric Serum 
Anti-Pneumococcic Serum 
Anti-Streptococcic Serum 
Antimeningitis Serum 

In the treatment of infections, both as a 
prophylactic and after the infection has been 
established, the bacterins, or bacterial vac- 
cines, suggested by Wright and others, are 
found very effective. These are obtained 
either in aseptic syringes, each representing a 
single dose, or in ampules containing several 
doses. They are as follows: 

Acne-Bacterin 

Coli-Bacterin 

Friedlander-Bacterin 

Neisser-Bacterin (Gonococcus Vaccine) 

Neisser-Bacterin Mixed 

Cholera-Bacterin 

Diphtheria-Bacterin 

Influenza-Bacterin Mixed 

Meningo-Bacterin 

Neoformans-Bacterin 

Plague-Bacterin 

Pneumo-Bacterin 

Pneumo-Bacterin 

Pulmonary Bacterin Mixed 

Pyocyano-Bacterin 

Scarlatina-Bacterin 

Scarlatina Bacterin Immunizing 

Staphylo-Bacterin 



34 THE HYPODERMIC SYRINGE. 

Staphylo-Acne Bacterin 
Staphylo-Albus Bacterin 
Staphylo-Aureus Bacterin 
Staphylo-Bacterin Mixed 
Staphylo-Strepto-Bacterin Mixed 
Strepto-Bacterin 
Typho-Bacterin 
Typho-Bacterin Immunizing 
Typho-Bacterin Mixed. 

Normal Horse Serum, the Tuberculins and 
other biologic products are employed hypo- 
dermically, as well as otherwise. 

The hypodermic has made possible many 
special drugs and chemicals which would not 
be of worth otherwise, or at Least, only slightly 
so. Among those recently introduced, and one 
which has been employed to a very consid- 
erable extent is arsenobenzol, or 8 -in. 

In the following chapters an effort will be 
made to give a full history, with application, 
of practically all agents employed hypo- 
dermically. 






CHAPTER V. 

Drugs and Chemicals. 

Apomorphine — Internally, apomorphine is 
employed as an expectorant and hypnotic, 
while hypodermically its chief office is that of 
an emetic, and it is for this effect that the 
drug is employed by the latter method. It 
is by far the best emetic we possess, when 
prompt reaction is desirable. The emetic dose, 
hypodermically is from 1-20 to 1-10 grain, 
based upon the age and condition of the 
patient. The fact that it is purely emetic and 
produces very little, if any subsequent nausea, 
makes it doubly valuable. It is employed in 
emptying the stomach in poisoning and suffo- 
cation, to relieve an overloaded stomach, or 
that of the alcoholic in delirium tremens or 
to dislodge foreign bodies from the throat or 
esophagus. It is likewise useful in the treat- 
ment of spasm and of hysteria. 

It should be remembered that apomorphine 
in itself, has more or less depressing action, 
and in marked narcosis it should be employed 
with care, lest it increase the condition. In 
opium poisoning, where the narcosis is very 
deep, it is preferable to employ other emetic 



36 THE HYPODERMIC SYRINGE. 

than this. This likewise applies in some cases 
of alcoholism. The condition of the patient 
should be considered at all times and the drug 
employed accordingly. 

The application is made either subcutaneous- 
ly or intramuscularly, as preferred, or as the 
conditions permit. In either instance the re- 
action is usually prompt and the physician and 
nurse should be prepared, prior to making the 
injection, with vessels ready to catch the vomit. 
The operator, should by preference, stand be- 
hind his patient, or to one side, as unpleasant 
accidents have occurred through the almost 
immediate action of the drug. Apomorphine 
gains its effect through central nerve action, 
and not through direct gastric contact, which 
accounts for its very mild or non-emetic effect 
when administered orally. 

Properly administered, with the conditions 
under consideration at all times, this agent is 
one of great value; in fact; in numerous in- 
stances, has proven a life saver, but it should 
be administered only when indicated. 

Atropine — It is probable that no other single 
drug offers the wide range of possibilities that 
does atropine. It is equally active both in- 
ternally and subcutaneously, although for im- 
mediate effect the latter mode of exhibition 
is the preferable one. As a rule, when ex- 
hibited hypodermically, it is for a specific pur- 
pose, and the full dosage is used. 

Atropine is the basis of all secret cures for 
alcoholism, the fullness of the head which it 



THE HYPODEEMIC SYRINGE. 3? 

produces rendering the liquor effect disagree- 
able. 

Aphonia of the hysteric form is relieved by 
full doses. 

Atropine is of use in asthma with cool, moist 
skin and loose sputa. 

It sedates bladder irritability and checks 
nocturnal enuresis. 

In bronchitis it checks the bronchorrhea, 
with profuse flow of mucus, and relieves the 
irritative cough. 

A full dose acts to relieve spasm due to both 
billiary and renal calculi, eases the pain and 
allows of the passage of the stone. 

Given to effect, it will abort acute nasal 
catarrh and dry up the secretions. In this 
connection it may be given orally in broken 
doses to effect, or hypodermically in like 
manner. 

It increases the cerebral blood-supply for 
the time being and is temporarily of use in 
cerebral anemia, but by determining the blood 
to the surfaces is of probably greater use, in 
full dose, in cerebral congestion. 

In Asiatic cholera, cholera infantum and 
cholera morbus, through directly opposing ir- 
ritation of the vagus, it relieves cramps, pain 
and diarrhea. It likewise relieves the same 
symptoms in intestinal colic and is the best 
remedy in lead colic. 

Atropine is of use in combatting convulsions 
due to congestion, teething or whooping-cough, 
and allays irritation and overcomes cough, 



38 THE HYPODERMIC SYRINGE. 

spasmodic, sympathetic, nervous or asthmatic 
in form, and relieves irritation and stimulates 
respiration in croup. 

Through relieving irritability, it is useful in 
cystitis, especially the form due to "catching 
cold," which it acts to abort. 

It relieves the cerebral anemia in simple 
delirium; is useful in delirium tremens with 
insomnia, cyan old skin and eoma vigil, 

and to stimulate cerebral circulation and 
lieve insomnia in dementia. 

Atropine is useful during the sweating 
of dengue, if excessive or weakening and 
serves to check the e e How of nrin< 

diabetes insipidus, and to check th< 
flow in diarrln 

It aborts exudation in diphtheria and is of 
value to support the heart during the acute 
inflammation oi throat and tonsils in this dis- 
ease. 

Atropine relieves the spasmodic and neural- 
gic forms of dysmenorrhea, with dark f< 
discharge and crampy pains and chills an 
the best hemostatic in menorrhagia, as well as 
in puerperal hemorrhage, and is the best rem- 
edy for ovarian neuralgia. It seems to have a 
selective action upon the pelvic organs, as a 
whole, of the female. 

In dyspepsia it serves to cheek hyperchlor- 
hydria, to relieve gastralgia and overcome con- 
stipation through the paralysis of inhibition. 

Through overcoming spasm it is of value in 
all forms of dyspnea, consequently its useful- 



THE HYPODERMIC SYRINGE. 39 

ness in asthma and other involvements of the 
air passages with this as a symptom. 

It is useful in fevers to bring about delayed 
eruptions, for insomnia and low delirium, 
photophobia, hebetude, hemorrhages and to 
sustain the heart. 

In gastric conditions it relieves neuralgic 
pains of simple gastralgia, and stops the pain 
and vomiting of gastric ulcer and checks the 
production of acid. It is useful in stomach 
pains in gout. 

To dry up the secretions it would seem in- 
dicated in edema of the glottis, as well as in 
other edemas. 

As in acute nasal catarrh, atropine is in- 
dicated in hay fever to dry up the secretions. 
As a rule its action is only temporary in this 
condition. 

Atropine is useful in many forms of head- 
ache. It breaks up the attacks in excessive 
meat eaters, and is useful for pain over the 
eye, for photophobia, intolerance of noise or 
motion, those forms due to uterine or gastric 
irritation in young women and in those cases 
where the headache is accompanied by pale 
face and shrunken skin, with pulse small and 
contracted. 

It relieves the irregular rhythm and cardiac 
strain in heart disease. 

In hemorrhages of all sorts, as hematemesis, 
hemoptysis, hemophilia, rectal and puerperal, 
and the bleeding of hemorrhoids and to relax 
spasmodic sphincter in the latter, atropine is 



40 THE HYPODERMIC SYRINGE. 

of great value. In all forms of internal hem- 
orrhages its indications are marked. It acts by 
determining the blood to the surfaces, and for 
this reason, is likewise indicated in all internal 
congestions. 

Through bringing about relaxation, full 
doses may overcome strangulation in hernia. 

It will relieve the pain in herpes zoster. 

Combined with strychnine to steady the 
nerves, full doses will relieve the spasm in hic- 
cough. 

In hypochondria, for cerebral anemia, gen- 
eral relaxation and sexual atony and in 
hysteria, for convulsions, aphonia and the puer- 
peral form, and to strengthen the erection and 
relieve nervous dread in impotence. 

In acute attacks of influenza for the head- 
ache, and to overcome excessive sweating and 
to dry up other secretions, as in acute nasal 
catarrh. 

It is useful in insomnia due to prostration, 
low arterial tension, with contracted pupils and 
frontal headache and to those forms due to 
eyestrain. 

It may relieve intestinal obstruction through 
relaxation of spasm and relief of pain. 

During labor it stimulates uterine contrac- 
tions and lessens pain and tendency to hem- 
orrhage, and during lactation is useful in de- 
creasing over-flow of milk. It is useful in 
mastitis. 

Atropine is useful in most of the nervous 



THE HYPODERMIC SYRINGE. 41 

conditions, as laryngismus stridulus, locomotor 
ataxia, etc., in overcoming paroxysms. 

It may, in full dose, abort attacks of both 
lumbago and sciatica and should be given 
trial in both conditions, invariably by hypo- 
dermic, and at the seat of the pain. 

In mania it allays irritation, induces sleep 
and quiets delirium, and is indicated in nym- 
phomania, hypochondria, delusions of persecu- 
tion, and whenever it is desirable to stimulate 
the cerebral circulation. It relieves the con- 
stipation and low arterial tension in melan- 
choly. 

It brings out delayed eruptions in the erup- 
tive fevers, and is indicated to combat the de- 
pressed vital powers and low temperature in 
measles and in the sore throat of scarlatina. 

Atropine overcomes the pain and irritation 
in acute nephritis. 

A single full dose may abort attacks of neu- 
ralgia. It is indicated in the various forms, 
as sciatica, lumbago, uterine, ovarian, inter- 
costal, myalgia, gastralgia, tic, dysmenorrheal, 
and in spinal irritation. In otalgia in children 
with coryza. 

For the perspiration of an excessive nature 
in phthisis and other diseases, atropine usually 
gives prompt relief and is indicated in all con- 
ditions of this sort. 

As in acute inflammation of the nasal pas- 
sages, atropine is indicated to abort acute 
pharyngitis and to dry up secretions thereof, 
as well as to relieve the pain and fever. 



4U :i: HYPODERMIC SYRINGE. 

In phthisis it not only acts to check sw< 
ing, but relieves diarrhea and bronehorrhea, 

irritative cough and dyspnea. 

Theoretically, it should be indicated as an 
abortive agent in the initial stages of 
pneumonia, if given to full effect. It must, 
however, be administered early to have such 
effect, if this is a possibility. 

In scurvy and all other conditions with 
cessive action of salivary glands, atropin( 
of great value as a corrective and to limit 
the secretion. It likewise ove - the relaxa- 

tion in scurvy. 

It has been employed with some i in 

seasickness, and to prevent 

if given after bowels are thoroughly empl 

Atropine is indicated in local muscular 
of sphincter and in those spasmodic conditions 
due to hysteria, anemia and teethil 

For relaxed genitfl turnal emissions 

and lack of orgasm in spermatorrh 

In all cases of heal exhaustion, with low 
arterial tension. 

It is frequently a "life Baver n in syncope 
and collapse, and is given after initial d0864 
of nitroglycerine to prolong tl; bra] hy- 

peremia. 

It is said to be of value, when injected close 
to the wound, in tetanus. 

In tonsillitis, as in other inflammations of 
that neighborhood, if given early, will abort 
the attack. It must be given to effect, or until 



THE HYPODERMIC SYRINGE. 43 

the throat feels dry, in order to gain such 
effect. 

Atropine is indicated in typhoid fever with 
contracted pupils, low muttering delirium and 
weak heart, and in variola with low muttering 
delirium, prostration and delayed eruption. 

It is recommended for the neurotic vomiting 
of pregnancy. 

These are only a few of the indications for 
atropine. It is the one drug worthy of great 
study as to its therapeutic possibilities. 

The dose of atropine hypodermically is from 
1-150 to 1-50 grain. 

Aspidospermine — From quebracho. Aspidos- 
permine is indicated in the dyspnea of 
asthma, emphysema and other respiratory 
maladies, but is less useful in the dyspnea of 
pulmonary tuberculosis. It is also mentioned 
as an antipyretic in fevers and to stimulate 
respiratory action. It is said to stimulate res- 
piratory function and allow of greater endur- 
ance of physical action, as hill climbing. Shoe- 
maker says that it acts admirably to relieve 
cyanosis and in acute rheumatism and in acute 
serous inflammations, to sedate the pulse and 
lower the fever. Lawrence reports a case of 
double pneumonia in a child in which he says 
that it showed a decided improvement in the 
breathing and heart-action. 

In the treatment of asthma it is given in 
combination with morphine, pilocarpine and 
emetine. 



+4 THE HYPODERMIC SYRINGE. 

The hypodermic dose recommended is about 
1-20 grain, although larger doses have been 
given. 

Aconitine — There are a few who rashly em- 
ploy aconitine hypodermically, but those who 
have made a close study of this agent, say 
that this method should never be employed. 
The action of the drug orally administered is 
so prompt as not to warrant its use otherwise, 
and there are but few, if any, indications re- 
quiring greater promptness of action than is 
shown when the agent is given internally. It 
is mentioned in passing to emphasise this fact. 

Cactin — Cactoid — Cactina — Cactine — A con- 
centration from cactus grandiHorus. There is 
a wide diversity of opinion relative to the use- 
fulness of this product. These who have made 
laboratory experiments upon healthy animals 
say that it is wholly inactive, while those who 
have observed it clinically, in its action in sick 
humans, insist that it is a cardiac stimulant 
and tonic. Basing the use of the drug on the 
latter observations, it is well to give it con- 
sideration. It is said tc gain its effect through 
increasing the nutrition of the heart. At any 
rate, in the face of many clinical observations 
and reports, and despite the adverse laboratory 
claims, it should be tried in those cases where 
such an agent is indicated. The dose is from 
1-128 to 1-64 grain. 

Caffeine— The alkaloid of coffee, tea and 
several other allied plants. In small dose 



THE HYPODERMIC SYRINGE. 45 

caffeine stimulates the heart and raises arterial 
tension and also stimulates cerebral function 
through additional blood carried to the brain. 
It also stimulates respiration and increases the 
urinary flow. This drug is useful in those 
conditions where it is desirable to stimulate 
the functions mentioned, but care should be 
taken not to over-dose, in that reverse effect 
may follow, as large doses are followed more or 
less, by depression. Caffeine is of great use 
in heart failure; also in dropsies with low 
arterial tension. The hypodermic dose is from 
1-2 to 1 grain. 

Cocaine — This drug will be considered at 
greater length under a special chapter on local 
anesthesia. 

Codeine — This alkaloid of opium, with its 
salts, needs but little discussion, as its actions 
and uses are well known. As a sedative and 
antispasmodic, it is superior, in many ways, 
to its sister alkaloid, morphine. It does not 
so seriously impound the secretions, as does 
morphine, nor does it have the same paralyzing 
effect on the bowel. It is claimed that its use 
is not, as a rule, even though continued over a 
considerable time, followed by habit forma- 
tion, but this has not been proved, and con- 
sequently it should not, as is the case with all 
opiates, be administered continuously with the 
thought that it is harmless in this particular. 
Codeine may be employed in practically all 
conditions in which morphine is indicated. It 



46 THE HYPODERMIC SYRINGE. 

is indicated in the relief of pain, spasm and 
as a hypnotic. It is said to be of value in 
the treatment of diabetes mellitus instead of 
the whole drug opium. The dose of the sul- 
phate hypodermically, and also of the phos- 
phate is from 1-4 to 1-2 grain. 

Colchicine — The alkaloid of colchicum. This 
remedy is usually administered orally and for 
slow and continued effect, but v. it is 

desirable to rapidly increase the eliminating 
function of the intestinal glands, liver, kid- 
neys and skin, it may be given in full 
1-30 grain hypodermic illy. This is a very val- 
uable agent in toxemias of numerous vari< 
in that it favors prompt elimination of the 
toxins stored within the blood and & Tt 

is indicated in rheumatism, gout; in (act in all 
toxic conditions, due to Faulty elimination. 



CHAPTER VI. 

Drugs and Chemicals 

(Continued) 

Condurangin — While this agent has been 
recommended for the cure of cancer, especially 
that of gastric variety, the results attending 
its use have not been such as to warrant its use, 
as a cure. It does, however, in full dose relieve 
the pain of both gastris cancer and ulcer, and 
is said to have been curative in several cases 
of the latter, after having been employed over 
a considerable time. As its action is purely 
local it must be exhibited hypodermically in 
external cancers. The hypodermic dose is 
given as 1-64 grain. 

Digitalin — While digitalis and all of its vari- 
ous products are invariably slow of effect, as 
a rule, it is claimed that the Germanic digitalin, 
administered in full dosage, gives a more or 
less rapid action, when exhibited hypodermi- 
cally. As all digitalis products act to a 
greater or less extent as gastric irritants, it is 
possible that digitalin may be administered, 
hypodermically, in the face of such irritation, 
with success. For rapid cardiac stimulation 
it is probable that other agents are far more 



48 THE HYPODERMIC SYRINGE. 

effective. The hypodermic dose is given as 
from 1-64 to 1-12 grain. The indications for 
the use of digitalis are too well-known to re- 
quire attention in these pages. There are a 
number of other digitalis products manufac- 
tured for hypodermic use, each claiming super- 
iority in one way or another. 

Emetine Hydrochloride. — This drag is one 
of the latest drugs to be employed hypodermi- 

cally. Dr. Leonard Rogers of Calcutta, alter 
employing it instead of the whole drag, ip« 
gave two reports of his findings in its applica- 
tion in the treatment of amebic dysentery. 

These appeared in The British Medical Journal 
in 1912, June 22 and Auirust 24. Even though 

patients were practically moribund when f 
ment was instituted, satisfactory results, with 
recovery followed. lie also found that the 
drug in this form could be exhibited without 
the nausea and vomiting incident to the use 
of ipecac; that is, when the agent was em- 
ployed hypodermically. There were, of course. 
some failures reported, but in the main the 
treatment was an improvement on all others 
hitherto employed. Since the initial reports 
made by Rogers, several other writers have re- 
ported like results. The description of the 
use of emetine hydrochloride, as given by 
Rogers is as follows: "I began with one-third 
grain doses, equal to 30 grains of ipecachuana, 
but now use half or two-third-grain doses in 
adults, while one-third of a grain may be given 



THE HYPODERMIC SYRINGE. 49 

with perfect safety in children of about eight 
years of age. I have several times given as 
much as a grain at once two or even three 
times a day in adults, and have never seen any 
depression or other alarming symptoms follow 
its use. Very occasionally severe pain may re- 
sult at the seat of injection, but this is quite 
exceptional, and there is usually no sign of 
any local reaction. Half a grain twice a day 
gives uniformly good results, or a larger dose 
once a day may be used if this is more con- 
venient." 

This drug is also employed in hepatic ab- 
scess with good results, such abscesses being 
due to the ameba of dysentery. It is probable, 
as time goes on that emetine will be found of 
use in other intestinal disturbances. Emetine 
is suggested, instead of ipecac, in the treat- 
ment of hemoptysis of tuberculosis, and several 
French authorities, among them Chauffard, 
Dopter, Rouget and Dufour have reported suc- 
cesses in this connection. Emetine, by the 
mouth, is recognized as having quite a wide 
range of application and it is possible that 
it will meet like indication when applied hypo- 
dermically. It is a drug well worth studying. 

Ergotin — Ergotoid (Liquid) — This extract 
of ergot has the same range of usefulness as 
have other forms of the drug, and that is 
rather a wide one. It is useful whenever it is 
desirable to stimulate non-striated muscle 
fiber. It acts to constringe the blood vessels 



50 THE HYPODERMIC SYRINGE. 

and consequently is useful, either alone or in 
combination with atropine, in the treatment of 
internal hemorrhages. It is indicated in con- 
gestions, especially cerebral of chronic form, 
and has been employed with good effect in 
epilepsy. It acts to overcome night sweats and 
has been found of use in whooping-cough. The 
particular variety of the product employed 
should have attention, as there are a number 
of different sorts marketed, and the dose varies 
to a very considerable extent. One particular 
sort should be accepted and employed to the 
exclusion of all others. Aqueous extracts are 
also employed hypodermically. As the dose 
varies, in the different soils, to such an extent, 
none will be mentioned at this time. 

Eucaine — This product will be given con- 
sideration in the chapter devoted to local 
anesthesia. 

Crotalin — The venom of the rattle snake. Is 
advised in epilepsy, but reports are meager and 
its use is not general. 

Gelseminine Hydrobromide — This salt of the 
alkaloid gelsemium is being employed to suc- 
ceed morphine in numerous instances and more 
especially in those cases where there is spinal ir- 
ritation. It is a marked antispasmodic and being 
relieved of its tetanic associate, gelsemin, gives 
very reliable effect. The isolation and segrega- 
tion of gelseminine has at last placed gel- 
semium among the list of worthy drug agents. 
Gelseminine is indicated in all fevers with 



THE HYPODEKMIC SYRINGE. 51 

nervous tension, bright eyes and flushed face. 
It exerts its action largely through the spinal 
cord. This agent should be given a trial, in- 
stead of morphine, when the latter is indicated. 
The hypodermic dose of the hydrobromide is 
given as 1-50 grain. 

Heroin — "While heroin is listed among the 
hypodermic agents by many of the makers of 
pharmaceuticals, we question its desirability 
in this connection. It is a drug which is more 
or less uncertain in effect, and even small doses 
may be followed by symptoms of opium poison- 
ing. Codeine fills all of the indications of 
heroin and in our mind, is far safer. If em- 
ployed at all, the action of heroin should be 
watched very closely, the patient being under 
the eye of the doctor or nurse at all times, and 
with antidotes at hand for prompt administra- 
tion. The dose of the hydrochloride salt is 
given as from 1-24 to 1-6 grain. 

Corrosive Sublimate — This will be con- 
sidered, with other mercurials, in a special 
chapter. 

Hyoscine — It is probable that we have no 
better drug hypnotic at our command than 
hyoscine. It is likewise an admirable sedative 
and to some slight extent, antispasmodic. It 
acts to produce a practically normal slumber, 
and that within a very short time after its ad- 
ministration. A dose of 1-100 grain of the 
hydrobromide salt is usually followed by sleep 
lasting several hours, from which the patient 



52 THE HYPODERMIC SYRINGE. 

awakens as from normal slumber, refreshed. 
Hyoscine is superior in every way as a 
hypnotic, to morphine, or in fact any of the 
other opiates, in that it does not interfere with 
the eliminative functions. It also has the ad- 
vantage that it may 1 e administered over a 
long period without the least tendency to habit 
formation, the patient being able to drop it 
immediately and entirely when there are no 
further indications for its use. Combined with 
morphine, and administered prior to volatile 
anesthetics, it acts admirably to obtund the 
sensibilities of the patient and, subsequent to 
operation, assure him several hours peaceful 
slumber. In this connection, hyoscine will be 
given greater consideration in a succeeding 
chapter. 

Hyoscyamme — Hyoseyamine is the sister 
alkaloid of hyoscine, from henbane. It is only 
mildly hypnotic but is markedly antispasmodic. 
As a rule it acts with considerable rapidity 
when administered orally, and to such an ex- 
tent as to render it hardly necessary of hypo- 
dermic exhibition. However, if it is desirable, 
it may be employed by the latter method. As 
an antispasmodic, hyoseyamine is preferable 
to opium or any of its alkaloids. It does not 
interfere with elimination; in fact, in some 
cases rather favors such function, and more 
especially when spasm is the interfering factor. 
Orally, in combination with nitroglycerine, it 
acts with considerable rapidity, sufficiently so 



THE HYPODEKMIC SYKINaE. 53 

under ordinary circumstances as not to require 
its hypodermic use. The dose of hyoscyamine 
sulphate is given as from 1-100 to 1-60 grain. 

Mercury Succinimide — This salt of mercury 
will be considered in a chapter devoted to the 
various mercurials. 

Morphine — Being so well known, morphine 
needs but little discussion in these pages. It 
was the first drug to be employed to any great 
extent hypodermically, and it has really es- 
tablished a bad reputation for this method of 
drug application, as he who employs the hypo- 
dermic syringe under ordinary circumstances 
is invariably suspected of using this particular 
drug. Morphine has really made many un- 
scientific physicians. This drug has its place, 
and when properly employed, is of great value, 
but as a rule we possess other agents which are 
preferable in all ways. Morphine acts to 
destroy function, and especially of elimination, 
to a considerable extent, and consequently 
favors toxemia. However, in emergency its 
use should not be refused. The dose, hypo- 
dermically, is from 1-8 to 1-4 grain. 

Nitroglycerine — Glonoin — Trinitrin — Al- 
though the action of nitroglycerine is very 
rapid when absorbed from the buccal mucous 
membranes, probably more so than w r hen ex- 
hibited hypodermically, there are instances 
when the drug must be employed by the latter 
method. This is true when a patient is in syn- 

The drug acts to stimu- 



:,4 THE HYPODERMIC SYBING 

late the heart through dilatation of the capil- 
laries and relieving the overburdened cardiac 
organ. It also acts to overcome syncope 
through the allowance of greater quantities of 
blood to the brain. As an initial remedy in 
the treatment of collapse, it paves the way to 
atropin, the latter maintaining the effect of the 
glonoin. It likewise acts well in combination 
with hyoscyamine to relieve spusm. Nitro- 
glycerine is effective in the treatment of spasm 
due to congestion, especially of the internal 
organs, and acts I it to the truer 

antispasmodics. When admi] 1 according 

to marked and recognized indications, nitro- 
glycerine is a very valuable "life saver." The 
dose ranges from 1-500 to 1-60 grain. 

Nuclein — The theory Tor the o uuclein 

is that it reinforces the white blood-eells and 
increases their force to combat with infective 
agents. Whether or not this is true, i1 
that improvement follows its exhibition in 
some infections. There are reports of marked 
improvement following its intravenous applica- 
tion in pulmonary tuberculosis. It is an agent 
which should be employed upon theory in all 
infections, and more especially in those with 
little or no leucocytosis. The dose ranges as 
high as 60 min. intravenously. This agent, in 
any amount, seems harmless. 

Physostigmine (Eserine) — Eserine increases 
peristalsis and relieves flatulence. It is em- 
ployed hypodermically w T here, for one reason 



THE HYPODERMIC SYRINGE. 55 

or another, the oral exhibition is prohibited. 
Small doses increase arterial tension. The 
hypodermic dose is given as from 1-100 to 1-50 
grain of the salicylate. 

Picrotoxin — The active principle of fish 
berry. Relieves the night sweats in phthisis. 
Is also useful in paresis, nervous debility, 
chorea and paralysis agitans and may be ap- 
plied in epilepsy. Has some of the actions of 
physostigmine, but does not cause nerve irrita- 
tion. The hypodermic dose is 1-50 grain. 

Pilocarpine — This alkaloid of jaborandi is 
our most powerful and rapid sudorific. For 
prompt depletion, it is indicated in edemas and 
dropsies. A full dose of from 1-10 to 1-5 grain, 
of the nitrate, hypodermically, may save life 
in edema of the glottis, when all other remedies 
would undoubtedly show failure. In using 
pilocarpine it should be remembered that the 
remedy is a most powerful depressant, hence 
the subject for treatment should be studied 
carefully, prior to any application of the agent 
being made. In dropsies, where other than 
very prompt action is desired, it is probable 
that apocynin is preferable to pilocarpine. 
However, under the proper indications, pilo- 
carpine is the drug parexcellence, and its use 
should not be refused at such times. The dose, 
hypodermically, is from 1-12 to 1-6 grain. 

Quinine and Urea — This combination will be 
given consideration in a chapter devoted to 
local anesthesia. 



56 THE HYPODERMIC SYRINGE. 

Scopolamine — The actions of scopolamine 
are practically identical with those of hyoscine. 
and it is employed instead of the latter by 
some. We believe that a chemically pure 
hyoscine is the preferable agent when either 
is indicated. The dose is the same as of hy- 
oscine. 

Sparteine — An alkaloid from broom. Spar- 
teine acts with rapidity, manifesting its e£ 
within fifteen to twenty minutes; an a the 

heart energy; induces regularity of cardiac 
action; has no appreciable effect upon the 
blood-pressure. Germain eine 

sulphate that it: "1. — it relieves the and 

pulse. It has a tonic action infinitely more 
marked, more prompt and more permanent 
than digitalis. 2. — It has an immediate 
ularizing effect upon the rhythm of a troubled 
heart. 3. — It accelerates the movement of the 
heart. " It is valuable in mitral lesions and 
where the cardiac action is weak and irregular. 
It is particularly indicated in tobacco heart, 
exophthalmic goiter and rheumatic heart. It 
is preferable to digitalin when quick effect is 
desired. It is useful in the reduction of cardiac 
dropsies. It is eliminated by the kidneys with 
comparative rapidity and has but little if any 
tendency to accumulation. The dose of the 
sulphate is from 1-8 to 1-2 grain. 

Strychnine — This alkaloid of mix vomica is 
so well known that nothing that could be said 
in these pages would add to the knowledge of 



THE HYPODERMIC SYRINGE. 57 

a single reader. It should, however, be given 
only when indicated, as it is an agent which 
is subject to more or less abuse. It should 
be remembered that strychnine is a good syner- 
gist in combination with the antispasmodics, 
through its ability to increase function. Like 
trinitrin, we should never be without it. 

Veratrine — While veratrine is more or less 
irritant, when employed hypodermically, it is 
indicated under certain conditions. In puer- 
peral eclampsia it is a very valuable remedy 
and should be pushed to full effect. In pneu- 
monia and other inflammations, where the 
elimination is being interfered with, veratrine, 
in that it serves to rapidly flush the capillaries, 
is the indicated remedy. As it is very rapid of 
action when administered orally, in small 
quantities and at frequent intervals, unless the 
patient is unconscious or delirious this mode, 
in the majority of instances, is preferable. The 
hypodermic dose of the hydrochloride salt is 
given as 1-64 grain. 

As the alkaloids are studied many others will 
undoubtedly be found eligible for hypodermic 
use, and as time goes on it is very probable that 
this method of drug exhibition will be em- 
ployed, practically to the exclusion of ail 
others. The agents above mentioned are only 
those which are more commonly in use at the 
present time, in so far as the active principles 
of plant drugs are concerned. 



CHAPTER VII. 

Mercurials. 

At the present time we find many of the 
salts of mercury employed in the treatment of 
syphillis, as well as other diseases, by the hy- 
podermic method. While it will not be our 
attempt to go into detail relative to the appli- 
cations of these various salts, the dose and ap- 
plication, in brief, of each will be given. 
Reference is made to Merck's Index, 1907, rel- 
ative to this class of chemicals. 

Mercury Aminopropionate (Mercury Alanin) 
— Alterative and antisyphilic. Hypodermic 
dose 1-12 to 1-6 grain. 

Mercury Anilinate — Antisyphilitic. Injected 
intramuscularly in 30 — 35 per cent, suspension 
in petrolatum. 

Mercury Asparaginate — Used in treatment 
of syphilis. Hypodermic dose 1-12 to 1-6 
grain per day. 

Mercury Benzoate (Mercuric) — Used in 
syphillis and skin diseases. Merck gives the 
hypodermic dose as follows: 15m 1 c.c. of 
solution of 0.25 mercury benzoate, 0.25 sodium 
chloride, and 30 water, per day. 



60 THE HYPODERMIC SYRINGE. 

Mercury Bichloride — Used in syphilis, 
chronic rheumatism and skin diseases. Merck 
gives the following formula for making up a 
solution for hypodermic use: 

Mercuric Chloride 0.1 Gm. 

Sodium Chloride 1. Gm. 

Water 100. C. C. 

M. Sig. Use 8 to 15m for each injection. 

Mercury Cacodylate (Mercuric) — Used in 
syphillis and was claimed at one time to be a 
specific and rapid cure. The dose for intra- 
muscular injection is 1-2 grain per day. 

Mercury Cyanide (Mercuric) — Used instead 
of the bichloride 1 and said to be less irritating. 
Indicated in syphillis, diphtheria and mem- 
branous croup. The hypodermic dose is given 
as 1-12 grain. 

Mercury Diodosalicylate (Mercuric)— Used 
in syphillis. Applied intramuscularly in 10 
per cent, suspension in liquid petrolatum. 

Mercury Ethylchloride— Used instead of 
mercuric chloride as an injection, and in the 
same indications. 

Mercury Glycocholate— Indicated in syphilis. 
Made up in stable solution, the dose of which 
is 8 to 15m every second day. This represents 
1-12 to 1-6 grain of mercuric oxide. 

Mercury Iodate (Mercuric)— Antisyphilitic. 
Subcutaneous dose 1-6 to 1-4 grain every 2nd 
or 4th day. 



HYPODERMIC SYRINGE 61 

Mercury Lactate (Mercurous) — Indicated in 
syphilis. Hypodermic dose 15m of a 1 per 
cent, solution daily. 

Mercury Oxide Yellow (Mercuric) — Anti- 
syphilitic. Exhibited intramuscularly, every 
8 days, 1 c.c. of suspension of 1:30 in olive oil. 

Mercury Resorcinolacetate — Antisyphilitic. 
Merck gives the method of hypodermic admin- 
istration as follows: 3m of a solution of 85 
grains of the salt in 85 grains of liquid paraffin 
and 30 grains of anhydrous lanelin, twice week- 
ly, the mixture to be warmed to 25 °C. before 
use. 

Mercury Salicylate (Basic Mercuric) — Anti- 
syphilitic, antigonorrheal, alterative. Hypo- 
dermic dose 1-3 grain, and maximum dose per 
day, 1 grain. 

Mercury Succinimide (Mercuric) — Anti- 
syphilitic and alterative. Hypodermic dose 1-5 
to 1-3 grain. 

Mercury Thymolacetate. (Mercuric) Indi- 
cated in syphillis, tuberculosis, etc., and inject- 
ed intramuscularly, l 1 /? grains in liquid para- 
ffine or glycerin every 3 to 5 days. 

Mercury Thymolate (Mercuric). Indications 
and uses same as of the Thymolacetate, the 
latter being preferable. 

Mercury Thymolnitrate. (Mercuric). Indi- 
cations and uses same as of thymolacetate. 

Mercury Thymolsalicylate. (Mercuric). In- 
dications and applications same as of thymo- 
lacetate. 



62 THE HYPODERMIC SYRINGE. 

Mercury Tribromphenolacetate. (Mercuric). 

Antisyphilitic, and used hypodermically in 
syphilitic joint diseases, in scrofula and tuber- 
culosis. Merck gives the dose as follows: 8m 
of a mixture of 100 grains of mercury tribrom- 
phenolacetate, and liquid paraffin 4V2 drams 
once a week. 

Mercury and Ammonium Bichloride. (Mer- 
curic). Antisyphilitic and alterative. Hypo- 
dermic dose, 1-3 grain in 8m of water. 

Mercury in oil, in various strengths is also 
employed hypodermically. 



CHAPTER VIII. 

Antitoxins and Serums. 

In the discussion of biologic products, em- 
ployed hypodermically in the treatment of dis- 
eases of an infectious nature, in view of the 
fact that there has been gathered together in 
the Mulford Working Bulletins, and that such 
matter is wholly of a scientific nature, we shall 
quote largely therefrom. 

Diphtheria Antitoxin. — The mode of prepar- 
ation will not be entered into at this time, as 
it is so well known as not to require comment. 
Suffice to say that since the introduction of this 
agent the mortality from diphtheria has be- 
come practically nil. 

The technic of injection of antitoxins is sim- 
ilar to that of all other hypodermic operations. 
The serum may be administered either subcu- 
taneously or intravenously. The latter method 
is preferable when prompt action is desired. 
Early in the history of diphtheria antitoxin 
the dosage was comparatively small, but today 
we see 10,000 or more units given initially, and 
in many instances such single large dose suf- 
fices. At an early date the serum was not con- 
centrated and more or less trouble followed the 



64 THE HYPODERMIC SYRINGE. 

exhibition of large closes on that account. To- 
day, with the highly concentrated antitoxin, a 
large dose is possible without discomfort to the 
patient. The preferable site for subcutaneous 
injections is beneath the left scapula. The an- 
titoxin should be employed at the earliest pos- 
sible moment; in fact, injected upon suspicion. 
When this has been done it has been the ex- 
perience that, with the infection present, the 
attack has been largely mitigated in fury be- 
cause of such prompt action. Antitoxin, in 
dose of 1000 units, should invariably be inject- 
ed in all persons who may have been in contact 
with the patient prior to, or who are to be his 
attendants, in that they may be immunized 
against the infection. It has been shown that 
such immunizing doses are very effective. 

In mild cases, if treated early, the dosage 
ranges from 3000 to 5000 units, while in severe 
cases it ranges from 7,500 to 10,000. If a sin- 
gle dose shows no apparent improvement in 
from 6 to 8 hours, a second dose of like num- 
ber of units should be given and a third repe- 
tition at like interval, if required. Age and 
condition of patient have but little to do with 
the dosage, in fact infants and feeble adults, 
being more prone to lack of immunity, require, 
and do well, on large dosage. The robust may 
not require as much of the antitoxin as do the 
feeble or young, because of their greater vital- 
ity and ability to combat the infection. 

When employed as a prophylactic, too small 
doses should not be administered, not less 



THE HYPODERMIC SYRINGE. 65 

than 1000 units, as 500 will not afford entire 
immunity. 

In the treatment of the established disease, 
it should invariably be remembered that half- 
hearted measures should never be resorted to, 
but that full dosage, and that only, as a rule, 
and at an early stage, will be effective. Also 
that the large initial dose not only acts in a 
curative manner, but overcomes the tendency 
to subsequent paralysis. 

Tetanus Antitoxin. — Tetanus antitoxin is ad- 
ministered in the same manner as is the diph- 
theria serum. However, today we find the in- 
travenous method gaining in popularity. This 
product is employed both for its prophylactic 
and curative effects. For the former action the 
serum is administered as soon as possible after 
suspected infection has accurred, and prior to 
the expiration of the period of incubation. It 
has been found that, when exhibited thus early, 
the antitoxin exerts an immunizing effect. Im- 
mediately, or as soon as possible after a wound, 
considered suspicious, has been received, the 
immunizing dose of 1500 units should be ad- 
ministered, and at the same time the wound it- 
self should be freely incised and opened to the 
air, in that the tetanus germs may have a poor 
ground upon which to grow, they being, as is 
known, anaerobic. The wound should be 
treated antiseptically and tincture of iodin ap- 
plied. If there is reason to believe that any of 
the tetanus organisms have been retained with- 



66 THE HYPODEEMIC SYRINGE. 

in the wound as shown by continuous suppura- 
tion, a second like dose should be administered 
at the end of eight days. If the condition has 
passed into one of true tetanus, immunization 
is out of the question, and the curative dose of 
the antitoxin administered. As with the diph- 
theritic serum, the initial dose should be large, 
from 10,000 to 20,000 units and repeated at in- 
tervals of from four to six hours and continued 
until all symptoms of tetanus disappear. Te- 
tanus antitoxin may be administered by injec- 
tion within the spine, and it is said that good 
results have followed this method. The re- 
ports, however, are meagre at present. If the 
toxin has not united too thoroughly with the 
nerve tissues, prior to the use of the antitoxin, 
good results, it is said will follow. This com- 
plete union has had much to do with the fail- 
ures reported, as the antitoxin is powerless to 
break up such union when once thoroughly per- 
fected. However, the antitoxin is the only real 
specific we have in this condition, and it should 
invariably be employed, regardless of the fact 
that it sometimes fails. With the adoption of 
the large dose it may prove of still greater 
value. 

Anti-Dysenteric Serum. — With the recogni- 
tion that dysentery was due to bacterial origin, 
steps were taken to perfect a serum of an anti- 
dysenteric nature. Relative to this serum and 
its application we quote from an article on the 
subject by Dr. Frederick P. Gray, which ap- 



THE HYPODERMIC SYRINGE. 67 

peared in the University of Pennsylvania Med- 
ical Bulletin, November, 1902, as follows: 

''There is no longer any doubt as to the ex- 
istence of a form of dysentery which is specific 
in the full sense of the term. The particular 
bacillus isolated by Shiga (Central bl. f. Bakt. 
u. Parasit. 1898, xxiii, 599) in Japan, now dem- 
onstrated to be the cause of the disease, chiefly 
through the researches of Dr. Flexner (Phil. 
Med. Jour. 1900, vi, 414) and his pupils, has 
been shown to be the cause of acute and suba- 
cute dysentery of the tropics and institutional 
epidemic diseases in temperate climates. Con- 
firmatory evidence relating to its etiological 
role has come from Germany and Holland 
(Kruse: Deut. med. Woch. 1900, xxvi, 637; 
1901, xxvii, 370; Spronk (quoted by Kruse): 
Deut. Med. Woch. 1901, xxvii, 370), and Duval 
and Bassett (Am. Med. 1902, iv, 417) have re- 
cently established the causal relation between 
the bacillus and the summer diarrhea of in- 
fants. 

"The importance of a pathogenic organism 
so widespread and with such varied capabil- 
ities as is exhibited by the bacillus of dysentery 
cannot well be overlooked. The prevalence of 
bacillary dysentery in the tropics and the 
marked susceptibility to the disease presented 
by a foreign population in those regions makes 
an attempt to check its progress, on the one 
hand through vaccination of those exposed to 
the infection and on the other through a spe- 
cific therapy, a desideratum well worth accom- 



68 THE HYPODERMIC SYRINGE. 

plishing. And now that the destructive enter- 
ocolitis of summer origin in children can be 
ascribed to a similar form of infection, the pro- 
curing of a curative serum will constitute noth- 
ing less than a great boon to humanity. M 

Preparation of Anti-Dysenteric Serum. — In 
the preparation of the anti-dysenteric serum, 
horses are immunized by inoculation with the 
several strains of dysenteric bacilli — Shiga, 
Flexner, Kruse and Duval — and the sera pro- 
duced are indicated by these names. The meth- 
od of immunization is similar to that employed 
in the production of the diphtheritic and tetan- 
ic antitoxins. During the earlier days of pro- 
duction of anti-dysenteric serum, that drawn 
from horses immunized for four or five months 
was employed, but it was found to be relative- 
ly weak in curative action, and Kinyoun in- 
sisted that it required at least 11 months im- 
munization of the horse prior to the time that 
a serum of therapeutic value could be obtained. 
Today the various sera employed are obtained 
from animals immunized for a period of much 
greater time, and such sera are found to be 
practically invariably active therapeutically. 

Protective Power of Immune Serum Against 
Living Cultures of B. Dysenteriae. — Again 
quoting from the article by Gray, we obtain the 
following information: 

"In the following experiments the serum 
used was taken with sterile precautions and in- 
oculated into the guinea-pig without addition 
of a preservative. Inoculations into the loose 



THE HYPODERMIC SYRINGE. 



subcutaneous tissue of the back have been used 
unless otherwise stated. 

"The protective power of the different im- 
mune sera were tested against multiple M. L. 
D. of living dysentery organisms. Repeated 
experiments prove that no protection against 
the dysentery organism is afforded by normal 
horse serum, and that perfect protection is af- 
forded by previous subcutaneous injections of 
the serum of a horse immunized against the 
strain of B. dysenteriae used. Identical spe- 
cific protection is shown by the sera of horses 
immunized with vaccines of the other three 
strains of B. dysenteriae, as shown by Tables 
I, II, III. 

TABLE I. — Protective Power of Serum from Horse 
"Kruse" (Treated for Five Months) against Kruse 
Strain of B. Dysenteriae. 



Weight 

of 
guinea 

pig. 

270 

260 

250 

240 

285 

250 



Dose of 
serum 

24 hours 
before 

Control 
6 c.c. 



■Strain 
of B. 
dysen- 
teriae. 
Kruse 



Intra- 
perit 
M. L. D. 
5 
5 
5 
5 
5 
5 



Result. 
Dead 18 hours 
Recovered 



TABLE II. — Protective Power of Serum from Horse 



"Shiga" (Treated for Five 
Strain of B. Dysenteriae. 



Months) against Shiga 



Weight 

of 
guinea 

pig. 

265 

280 

275 

275 

290 

250 

265 

265 



Dose of 
serum 
24 hours 
before 
Control 
6 c.c. 



Strain 
of B. 
dysen- 
teriae. 

Shiga 



Intra- 
perit 
M. L. D. 
3 
5 
5 
5 
5 
5 
5 
5 



Result. 
Dead 18 hours 
Recovered 



70 THE HYPODERMIC SYRINGE. 



TABL.E III. — Protective Power of Serum from Horse 
"Flexner" (Treated for Five Months) against Flexner 
Strain of B. Dysenteriae. 



Weight 


Dose of 


Strain 






of 


serum 


of B. 


Intra- 




guinea 


24 hours 


dysen- 


perit 




pig"- 


before 


teriae. 


M. L,. D. 


Result. 


2DJ 


Control 


Flexner 


5 


Dead 20 hours 


300 


6 c.c. 


" 


5 


Recovered 


285 


11 


" 


5 


" 


285 


" 


11 


5 


M 


285 


" 


" 


5 




300 


" 


*• 


5 


" 


285 






5 




TABLE 


IV. — Amount of Flexner Se: 


rum Necessary 


to Protecl 


: against M. 


L. D. Intraperitoneal^' of Flex- 


ner Strain. 








Weight 


Dose of 


Strain 






of 


serum 


of B. 


Intra- 




guinea 


24 hours 


<1> sen- 


perit 




pig. 


before 


te i 1 1 


M. L. D. 


Result. 


250 


Control 


Flexner 


7 


Dead 20 hours 


250 


6 c.c. 


11 


7 


Recovered 


215 


4 c.c. 


•• 


7 


" 


250 


2 c.c. 


" 


7 


" 


230 


1 c.c. 


44 


7 


■ 



" These subcutaneous doses of protective 
serum have been mad<> intentionally large for 
the purpose of comparisons that are to follow; 
that the amounts used are far in excess of the 
quantity necessary to secure complete protec- 
tion is shown by Table IV." 

Protective Action of Immune Serum Against 
the Vaccines of B. Dysenteriae. — "In addition 
to their protective action against living cul- 
tures of the dysentery organisms, the immune 
sera are found to afford, as would be expected, 
distinct protection against the fatal toxic ef- 
fects of dysentery vaccine. 

"The protective power of the serum of the 
horse imperfectly immunized to the bacillus of 



THE HYPODEEMIC SYRINGE. 71 

dysentery against such bacillary inoculation of 
the guinea-pig can be taken as proven beyond 
peradventure. The experiments in which this 
fact is established are equally conclusive as re- 
gards infection through living organisms and 
intoxication through dead ones. Such success- 
ful results in the guinea-pig, in which the path- 
ological process is rapidly developed and quick- 
ly generalized in contradistinction to the slow- 
er evolution and localized character of bacil- 
lary dysentery in man, may be taken to augur 
well for the therapeutic application of the ser- 
um in the human disease. There is every rea- 
son for believing that a serum many times 
stronger and correspondingly more potent than 
that here described, will eventually be ob- 
tained. (Such a serum is now obtainable). 

"At this writing (October 1, 1902) evidence 
of considerably greater progress in respect to 
the immunization, as compared with the state 
existing three months previously, is at hand. 
(Now, in 1913, there are furnished sera from 
horses immunized one, two and more years. 
Two strains of the B. dysenteriae are employed 
in such immunization, the Shiga (Japan) and 
the Flexner (Manila), in order that we may 
possess sera known to combat the different 
types of infection, non-acid and acid.) 

"That the hope of successful application of 
such a serum therapy to man is not entirely 
speculative can be shown by a consideration of 
the published results by Shiga (Sei-I-Kwai, 
Med., Jour, Tokyo, 1901, xx, 89 ; Deut. med. 



72 THE HYPODERMIC SYRINGE. 

Woch. 1901, xxvii, 741, 765, 783) of the serum 
treatment of Japanese dysentery. While de- 
tails are not yet available, Shiga states that of 
250 cases treated with antidysenteric serum the 
mortality averaged 10 per cent, as against 
36 per cent, in cases treated by ordinary 
methods.' ' 

In the remarks upon the subject made in 
American Medicine, Sept. 13, 1902, relative to 
work done in the laboratories of the Thomas 
"Wilson Sanitarium and the Rockefeller Insti- 
tute for Medical Research, we find the follow- 
ing: 

14 A careful study of the bacterial flora of a 
number of cases was made and from forty-two 
typical cases of summer diarrhea we succeeded 
in isolating from the stools the bacillus dysen- 
teriae, Shiga. The specific organism was se- 
cured also from scrapings of the intestinal mu- 
cosa at autopsy, and in one case, from the mes- 
enteric glands and liver. The dysenteric bacil- 
lus was present often in large numbers in the 
stools of acute cases, but was secured with dif- 
ficulty from the cases of mild character and 
those of long duration on account of its pres- 
ence in relatively small numbers and the an- 
tagonism of the normal intestinal bacteria The 
specific bacilli isolated from different cases of 
the disease are identical, and agree in morphol- 
ogy, cultural features, pathogenic properties 
and reaction to specific serum with the dysen- 
teric bacillus isolated from cases of acute dys- 
entery in adults by Shiga in Japan, Flexner 



THE HYPODERMIC SYRINGE. 78 

and Strong in the Philippines, Krase in Ger- 
many and lately by Vedder and Duval in this 
country. Agglutinative reactions when the or- 
ganisms were tested, (a) with the blood-serum 
of the patients from whom they were secured, 
(b) with the serum of other infants suffering 
from summer diarrhea, (c) with the serum 
from adult patients with acute dysentery, (d) 
with anti-dysenteric immune serum. The spe- 
cific bacillus was not found in the stools of 
twenty-five healthy children, nor those suffer- 
ing with simple diarrhea, marasmus and mal- 
nutrition ; nor did the blood-serum of these lat- 
ter individuals agglutinate the dysenteric 
bacillus. 

"We believe our findings justify us in the 
conclusion that the summer diarrheas of infants 
are caused by intestinal infection with the bac- 
illus dysenteriae, Shiga, and therefore, are etio- 
logically identical with the acute bacillary dys- 
entery of adults. The cases studied, from 
which the dysentery bacillus was isolated, in- 
clude examples of so-called dyspeptic diarrhea, 
or enterocolitis and of malnutrition and mar- 
asmus with superimposed infection. 

In relation to the pathology of dysentery, 
and the preparation and results following the 
use of anti-dysenteric serum, the following is 
quoted : 

"Shiga (San. Rep. U. S. Marine Hosp. Serv. 
1897) in 1897 published the results of his in- 
vestigations on the epidemic dysentery in 



H THE HYPODEEMIC SYRINGE. 

Japan. He found the cause to be a bacillus, 
which he designated the Bacillus dysenteriae. 

"Flexner (Phil. Med. Jour. p. 414) and 
Strong (Rep. Surg-Gen. U. S. A., 1900) found 
what they determined to be the same organism 
in cases of acute epidemic dysentery occurring 
in the Philippine lslai 

"Kruse (J)eut. med. Woch., 1901, p. 370), in 
an exhaustive investigation found an organism 
isolated with acute epidemic dysenteries occur- 
ring in certain institutions in Germany. 

"Vedder and Duval (Jour, of Exp. Ped. 
1901) also made a study of dysentery in the 
United States and found the same organism. 
It has been found also in Puerto K 

"The distribution of this organism appe 
to be quite general, and there can be but little 
doubt at the present time but that it is respon- 
sible for nearly if not all, the >f acute 
dysentery of baeillary origin OCCUring in all 
parts of the world. 

"In a summary of a discussion before the 
Pathological Society of New York (Arch, of 
Ped. Nov. 1903) Professor Simon Flexner 
stated that there are two well-defined eroups of 
organisms isolated with dysentery in adults 
and children, the non-acid or Shiga group, and 
the acid, or Manila group. He believes that 
the future must determine what relation the 
non-acid or Shiga group, bears to the etiology 
of summer diarrhea in children. So far, his 
observations confirm the statements made by 
Vedder and Duval that the acid-producing 



THE HYPODERMIC SYRINGE. 75 

group predominates in the summer diarrheas. 
There seems to be a difference of opinion as to 
the importance which should be attached to the 
presence of the Shiga (dysentery) group of or- 
ganisms in its relation to summer diarrhea. 

"W. H. Park did not believe that the Shiga 
bacillus was present in the larger proportion 
of the summer diarrheas, as it has been his ex- 
perience that this organism is not found, unless 
there are distinct symptoms of dysentery where 
the discharges contain mucous and are tinged 
with blood. 

"Koplik regards the question as very com- 
plex, believing that the Shiga group is found 
in a limited number of cases. He reports that 
in the Babies' Hospital there were thirty-seven 
cases of summer diarrhea in which the dysen- 
tery bacillus was found. These cases were 
acute colitis, with bloody stools. 

"Knox's investigation, conducted at the Wil- 
son Sanitarium during the summer months of 
1903, reports that there was nothing very strik- 
ing in the character of the stools or patholog- 
ical conditions found in the autopsy to differen- 
tiate the cases in which the dysentery bacillus, 
acid type, was found from the ordinary typical 
summer diarrhea. He is inclined to believe 
that a large group of both acute and chronic 
cases will be found to be due to this organism. 

"Wellstein reports sixty-two cases of sum- 
mer diarrhea in infants from two months to two 
years old occurring during the three summer 
months. Of these sixty-two cases, forty-seven 



7i) THE HYPODERMIC SYRINGE. 

were found to be due to the Shiga bacillus. The 
mortality rate ranges from 55 to 78 per cent, 
according to the institution. In stools contain- 
ing much mucous and blood the Shiga bacillus 
was more readily isolated than when the con- 
trary obtains. 

"Cordis reports fifty-two cases studied with 
reference to the presence or absence of dysen- 
tery bacillus. Of this number, twenty-six cases 
showed the organism, twenty-five were of the 
acid group and one of the non-acid group. The 
blood of forty-five of tin- was tested for 

its agglutinating effect upon the organism, and 
in only ten was there any agglutination to both 
the Harris and Shiga types of bacillus. 

"Duval and Scorer report the results of their 
observations, conducted at the College of Phy- 
sicians and Surgeons, of Beyenty-nine eases 
summer complaint ranging from mild diarrhea 
to bloody iliocolitis with exudation. Examina- 
tion was made of the stools almost immediately 
after passing, and upon this they ascribe the 
large amount of success in isolating the bacil- 
lus of dysentery. Of this number the dysentery 
bacillus was isolated in seventy-five cases, or 
94 per cent. In fifty-eight cases of these the 
acid-producing type was found ; in five cases, 
both the acid and non-acid producing type, and 
in twelve cases, the Shiga type. Four cases 
were negative. 

1 'In 1902 forty-five cases of cholera infantum 
were examined by Duval and Bassett at the 
Thomas Wilson Sanitarium, Baltimore, and in 



THE HYPODERMIC SYRINGE. 77 

forty-two of these cases organisms were iso- 
lated which by their cultural characteristic re- 
action to the immune sera, were found to be 
identical with the Bacillus dysenteriae. In the 
beginning it was held by some that the organ- 
ism which had been isolated from these several 
groups of cases in various parts of the world 
were one and the same. This opinion was 
based on the morphologic agglutinating reac- 
tion with the blood of cases recovering from 
dysentery of that of an animal immunized 
against the bacilli. Lentz (Zeit. fur Hyg. 1902) 
shows that there are two well defined groups of 
these organisms, one of the Shiga alkaline type 
and the other of Flexner, or acid type. Dur- 
ing the summer of 1903 this subject was further 
investigated in this country with particular re- 
ference to its relation to summer diarrhea. 

"Shiga claims that this organism does not as 
a rule invade the tissues other than those of 
the intestinal tract. It may sometimes, however, 
be found in the mesenteric glands. This organ- 
ism in its growth in the intestinal tract secretes 
a virulent poison very much after the nature 
of the cholera spirillum. This has a dual ac- 
tion, one directly upon the intestinal coat and 
the other systemic. Recent investigations made 
by Shiga and Neisser show that this toxin of 
the dysentery bacillus can be isolated from cul- 
tures and when injected into susceptible ani- 
mals like the rabbit or guinea pig produces 
symptoms of paralysis and profound changes 
in the intestinal mucous membrane pf both the 



78 THE HYPODERMIC SYRINGE. 

small and large intestines. They believe that 
this poison, even when absorbed into the system 
from the intestine, is finally eliminated by the 
intestine. 

"From the observations made in this country 
during the past two years, it is dem »n-i rated 
beyond a doubt that cases of subacute bacillary 
dysentery occur throughout the whole year. 
This has been encountered in the dead of win- 
ter in the hospitals of Philadelphia and else- 
where. Epidemics of the dis( m to occur 
only when the conditions are ideal for its 
growth and development, and naturally the 
summer months offer the best conditions for 
development. 

"The mortality of dysentery varies consid- 
erably according to the time and place. The 
usual mortality accompanying the disease in 
Japan has never been duplicated anywhere, 
save, perhaps, among the troops of the late 
Civil War. In this reaped it is very difficult to 
ascertain from record, etc., the mortality of 
bacillary dysentery at this time b cause of i f 
being so recently under investigation with re- 
ference to its cause. No rep ve those of 
Wellstein, have so far been published regard- 
ing the mortality of cases of summer diarrhea. 
It would not be wise to draw a hard-and-fast 
conclusion from these cases because so far as 
observation goes, the majority of cases of chil- 
dren received into the hospitals of cities dur- 
ing the summer months, are in what may be 
said the last stages of the disease. Many cases 



THE HYPODERMIC SYRINGE. 79 

of summer diarrhea occuring in the private 
practice of physicians are exceedingly mild. In 
fact, the epidemics may be mild, but at other 
times they may be severe. The same may be 
said with regard to the dysentery of adults. 
Some of these epidemics are mild, while others 
may be severe. 

Pathological Anatomy. — "Howland examin- 
ed thirty-two cases. In five cases there was a 
pseudo-membrane in the colon and ilium. The 
membrane was composed of necrotic tissue and 
disintegrated cells containing countless bac- 
teria. Fibrin was present in small amount, if 
at all; there was necrosis of the mucosa. The 
necrosis did not extend beyond this coat. On 
the border of this necrotic tissue there were 
small hemorrhages with thrombosis. There was 
a line of sharp demarcation dividing the sound 
tissue by a zone of small round cell infiltration. 
Cells were of the mono and poly-nuclear type. 
A large number of "mast" cells were found 
around the small blood vessels. In another 
group (four cases) the mucous membrane was 
in good condition, the changes occurring al- 
most wholly in the lymph follicles. The spleen, 
as a rule, was not affected. The kidneys 
showed cloudy swelling. Cultures made from 
all the organs were negative as to the Shiga 
bacillus." 

Serum Therapy. — "Shiga reports that in 1119 
cases treated in the hospitals at Tokyo, there 
was a mortality of 28.5 per cent. During the 



GO THE HYPODERMIC SYRINGE. 

same time there were treated with the serum in 

1898 65 Cases. 

1899 91 Cases. 

1900 110 Cases. 



266 Cases, 
with a mortality of 9.6 per cent, as compared 
with those not treated 32.6 per cent. During 
the years of 1899 and 1900, 400 cases were 
treated. Those treated early and in the hos- 
pitals the mortality was 9 per cent., while those 
treated at their homes and in private practice 
the mortality was 12 per cent. 

"Koplik reports that eight cases of cholera 
infantum were treated with anti-dysenteric 
serum. In three of these there was a striking 
improvement soon after administration of the 
serum, in others there was no improvement. 

" Parke states that during the summer of 
1903 some experience in these cases and their 
treatment by serum was secured by the New 
York Board of Health. About fifty cases were 
under observation, and one-half of these were 
treated with serum. Some of the mild cases did 
not seem to be much improved by this treat- 
ment, although none of them became worse. 
Bad cases treated with the serum apparently 
did better than corresponding cases without 



serum 



During the summer of 1903 experiments 
were undertaken under the direction of Dr. 
Simon Flexner at Boston, New York and Balti- 
more with this serum. During the month of 



THE HYPODERMIC SYRINGE. 81 

May, 1904, an extensive use was made of anti- 
dysenteric serum in Southern countries and in 
the tropics, followed with most satisfactory 
results." 

Dosage. — c ' The same rule holds in the admin- 
instration of anti-dysenteric serum as with the 
anti infections serums and antitoxins, the ne- 
cessity of early administration of the serum in 
all cases, and where employed late in the dis- 
ease, large doses must be administered. 

"As a rule, in cases treated early 10 c.c. to 
20 c.c. of the serum should be administered 
every six to twelve hours ; in cases treated late, 
or of unusually severe type, 20 c.c. 

Antipneumococcic Serum. 

Anti-Pneumonic Serum. — See Pneumo-Bac- 
terin. 

Anti-Streptococcic Serum. — See Strepto-Bac- 
terin. 

Antimeningitis Serum. — Antimeningitis se- 
rum is prepared, as are other serums and anti- 
toxins through immunizing horses with steadily 
increasing doses of first killed, then living men- 
ingococci, until at the end of six months, if a 
dilution of 1 to 5000 of the serum of the ani- 
mal shows bacteriotropic power, it is of suffi- 
cient strength for therapeutic use. If such 
power is not exerted, the inoculations are con- 
tinued until this is attained. 

Dopter (Annales de L'Institut Pasteur, Vol. 
xxiv, 1910, p. 96) says that antimeningitis se- 
rum prepared by subcutaneous inoculation of 



. 



82 THE HYPODERMIC SYRINGE. 

horses with meningococci and autolyzed cul- 
tures, possesses the following properties: 

"1, It contains agglutinins specific for the 
meningococcus and also 'co-agglutinins' for the 
pseudo-meningococci (gonococci, etc.) as is 
shown by the saturation of these organisms by 
the agglutinins. 

"2. It contains precipitins, which .are 
shown when one mixes the serum, even in very 
high dilutions, with the extract of meningo- 
cocci. The mixture, left at room temperature, 
first becomes cloudy and then gives rise to a 
precipitate which collects at the bottom of the 
test tube. The same precipitate may be pro- 
duced with extracts of pseudo-meningococci 
(diplococcus crassus, gonocoecus, etc.). The 
test of saturation of complement shows that the 
precipitation in this case is a co-precipitation 
or ' precipitation in group.' If the serum is 
heated several times at 55° it loses in large part 
its power to produce precipitins. 

"3. It contains specific amboceptors, the ex- 
istence of which show by the test of deviation 
of complement. Deviation of complement may 
be produced equally well with a microbic emul- 
sion, or with the autolyzed culture. It can be 
effected only by the meningococcus; even the 
most closely related organisms give negative 
results.' ' 

Neufeld and Kraus say that the serum pos- 
sesses bacteriotropic powers and that the deter- 
mination of this is the basis upon which to de- 
termine the therapeutic power. It does not, on 



THE HYPODEEMIC SYRINGE. 83 

the other hand, possess bactericidal power. 
They determined the antitoxic powers by in- 
jecting, intraperitoneally, young guinea pigs 
with a mixture of the serum and autolyzed cul- 
tures, and found that, as a rule, 1 c.c. of serum 
would neutralize five fatal doses of the men- 
ingococci endotoxins. 

Not only is the serum of those horses immun- 
ized in the usual way of therapeutic value, but 
likewise is that of horses immunized by the in- 
travenous injections of living cultures. 

That antimeningitis serum is of great value 
in the treatment of cerebro-spinal meningitis is 
shown by the facts that it very markedly di 
minishes the mortality; that it influences the 
symptoms in practically every case in which it 
is used ; that it reduces the duration of the dis- 
ease, and practically overcomes any tendency 
to sequelae. 

Under the older lines of treatment, it is 
shown by statistics that the mortality in epi- 
demics has ranged from 30 to 80 per cent., with 
100 per cent in young infants. In one series 
of cases, reported by Flexner, in which the se- 
rum was employed, the mortality was only 25 
per cent. On the continent it is reported by 
some that the mortality has been reduced still 
farther, to 18.35 per cent. From 53 per cent., 
Schone reports a reduction to 27 per cent., and 
Jehle one from 80 to 45 per cent. In the epi- 
demic of 1909, in France, Dopter reported a to- 
tal of 402 cases, with 66 deaths, or a mortality 
of 16.44 per cent. Of the cases reported 19 of 



84 THE HYPODERMIC SYRINGE. 

those who died were in extremis when first in 
oculated with the serum, or death was due to 
other than directly to meningitis. Deducting 
these cases, the mortality was 12.27 per cent, in 
all other cases treated. Those cases treated 
without serum in the same epidemic showed a 
mortality of 65 per cent. All reports point to 
the fact that the early use of serum is followed 
by greater successes than are the latter ones. 

As a rule, after the intraspinal injection of 
the serum, and within twenty-four to forty- 
eight hours, there is a remarkable reduction of 
all symptoms. The temperature falls, and in 
some cases may fall to normal, with prompt de- 
fervescence, or the fall may be by lysis, and 
there is relief from headache, coma, insomnia 
and delirium and although stiffness of the neck 
usually persists to some extent, longer than do 
the other symptoms, it likewise shows early re- 
lief. In some instances there is slight rise in 
temperature after the injection, but this is, as 
a rule, followed by a prompt fall. With the 
other symptoms, the auditory and ocular phe- 
nomina disappear and the paralysis is over- 
come. The patient generally shows improve- 
ment, with disappearance of the facial pallor, 
the typhoid condition and signs of toxemia. 
The serum produces a marked effect upon the 
spinal fluid, the degenerated polynuclear cells 
are lessened and replaced by normal cells of 
that character, with a lessened number of men- 
ingococci, which finally completely disappear. 
Those remaining show disintegration. Finally 



THE HYPODEEMIC SYEINGE. 85 

cultures from the spinal fluid are sterile. The 
meningococci are absent and the polynuclear 
cells become less abundant and become gradu- 
ally replaced by mononuclear cells, with the es- 
tablishment of convalescence and recovery. 
That the spinal fluid returns to normal is like- 
wise determined by chemical test, showing the 
lessening of albumin, glucose, etc., contents of 
the fluid and by the disappearance of products 
of bacterial disintegration. This latter is shown 
by occurence of the precipitin reaction. Thai, 
the serum is beneficial is shown by the fact that 
in some cases, improvement takes place while 
the injections are being given, but that the 
symptoms reappear with the withdrawal of the 
serum, to again disappear when inoculations 
are resumed. In other cases, all the symptoms 
do not show coincident improvement; the tem- 
perature may fall, but the nervous symptoms 
remain; the general condition may show no 
marked change, may be even precarious, while 
those of a meningeal character may entirely 
disappear, and these suggest that some modifi- 
cations should be made in the treatment. 

Those cases which show but little improve- 
ment, or none at all, are those in which the con- 
dition is of the fulminant sort; those in which 
injection has been made late in the course of 
the disease; where the disease assumes the sep- 
tic type, as shown by hemorrhages and large 
petechiae and extra-meningeal complication, as 
broncho-pneumonia or nephritis ; those of a ce- 
rebral type, with the disease limited to the cran- 



THE HYPODERMIC SYRINGE. 

ial regions, and which are reached with diffi- 
culty with the serum by intraspinal injection; 
in those cases where, although the serum pro- 
duces improvement initially, the disease, after 
a time passes into the chronic stage and in 
those cases where the serum has no effect upon 
the meningococci in the cerebro-spinal fluid. 
Why this is so, is not clear. It is explained that 
it may be due to the fact that the lesions are 
located on the vertex or in the cerebral ven- 
tricles, and are not accessible to the action of 
the serum through direct contact. 

Prior to the use of the serum it was a com- 
mon thing to see cases lasting two, three and 
four weeks, whereas the average duration, since 
the introduction of inoculation has reduced the 
duration to from eight to twelve days, and with 
a return to the normal condition and without 
sequelae, as was the case under the older treat- 
ment. The reduction of duration has much to 
do with the lack of occurrence of sequelae. In- 
stead of a percentage of 23 sequelae, as report- 
ed by Netter, Dopter reports only 2.56 per cent. 
Under the treatment without serum deafness, 
blindness and paralysis were present following 
the disease in from 70 to 80 per cent. Netter, 
following the use of the serum, reports only 
7.5 per cent, of sequelae, and in 402 cases only 
6.2 per cent., and most of them lesions of the 
internal ear. No complications have been no- 
ticed which were not present prior to the first 
injection of the serum. 

The serum, introduced into the spinal canal 



THE HYPODERMIC SYRINGE. 87 

acts directly upon the meningeal lesion, and at 
a distance upon the general organisms. Local- 
ly it brings about modifications of the cerebro- 
spinal fluid, as is shown by disappearance of 
pus corpuscles, the presence of unlatered poly- 
nuclear cells and by the disintegration and final 
disappearance of the meningococci. The latter 
is believed to be due to bacteriolyitic power up- 
on the part of the serum, and it is likewise be- 
lieved that the serum neutralizes the endotoxin 
set at liberty in the fluid. Owing to the pres- 
ence of intact polynuclear leucocytes, many 
believe that the serum acts by stimulation of 
phagocytosis. That bacteriolysis occurs, is ex- 
plained by the occurence of intracellular diges- 
tion of the bodies of the leucocytes. The lib- 
erated endotoxin may be absorbed and de- 
stroyed by the same cells. 

The serum permeates the general organism 
through absorption from the membrane of the 
cord into the general circulation. According 
to Netter, in one case of meningococcemia, in 
which meningitis was not present, intraspinal 
injections of the serum were followed by satis- 
factory results. That other symptoms than 
those of the brain or cord, such as petechial 
eruptions, albuminuria, and others, disappear 
with the injection of the serum, are indicative 
of general absorption. 

That injections of diphtheria antitoxin and 
other sera have no effect in cerebro-spinal men- 
ingitis, and that antimeningitis serum has a 



88 THE HYPODERMIC SYRINGE. 

marked one in a curative way, is indicative 
that the latter is a specific in this disease. 

Method of Employment. — Quoting from 
Working Bulletin No. 8, we obtain the follow- 
ing data relative to the technic of application 
of antimeningitis serum: 

It has been shown that as the diffusion of 
fluids into the spinal canal is quite slow, the 
best results are obtained if the serum is inject- 
ed directly into this canal. In a few cases in 
which the symptoms were entirely cerebral and 
in which intraspinal injections produced little 
or no benefit, the attempt has been made to in- 
ject the serum through the open fontanels of 
young infants directly into the ventricles of the 
brain. But these experiments have been too 
few in number for any opinion to be expressed 
as to the efficacy of the procedure. It is per- 
haps worth trying in such cases as have been 
mentioned. 

All authors insist upon the necessity of using 
large doses, even in young infants. In the 
adult one may inject 20, 30, 40 and even 45 c. c. 
of serum, provided a similar amount has been 
withdrawn by lumbar puncture. In infants 
less than one year old, one may easily inject 10 
to 30 c.c. 

Except in mild attacks, one injection is rare- 
ly sufficient to effect a complete cure. After 
the first injection all the symptoms may im- 
prove so that one considers a second injection 
unnecessary and believes the patient is cured, 
but the next day, or the day after, there may be 



THE HYPODERMIC SYRINGE. 89 

a recurrence of fever and meningeal symptoms, 
and a fresh injection is necessary. This may be 
explained by the fact that the serum introduced 
into the spinal canal has been absorbed from 
this before its effect has been fully developed. 
Some authors give one injection, and if there is 
no improvement they repeat it until improve- 
ment is secured. If the symptoms continue to 
improve they give no further injections. Other 
authors consider that it is better to inject sys- 
tematically 20 to 30 c.c. of serum daily for three 
or four consecutive days, even when the first 
injection has produced marked improvement of 
the temperature and of the symptoms. Accord- 
ing to Netter, the repetition of injections pre- 
sents the greatest advantage of producing more 
cures and the shortening of convalescence, as 
well as lessening the tendency to recurrence 
and sequelae. A fall of temperature is not suf- 
ficient reason to believe that the dose of serum 
has been sufficient, as in a certain number of 
cases the other symptoms do not improve co- 
incidentally, and in some severe cases there is 
little fever. For this reason it is better to base 
the use of the serum on the other symptoms. 
The most valuable sign is the appearance of the 
cerebro-spinal fluid. If after the injection men- 
ingococci which have undergone degeneration 
are discovered, it is necessary to continue the 
injections. If after several daily injections the 
fluid contains no meningococci and the degen- 
erated leucocytes have been replaced by nor- 
mal, no further injections are necessary, even 



90 THE HYPODERMIC 8YEINOE. 

though the temperature does not fall. It is 
wise, however, to draw specimens of fluid for 
examinations, at intervals of several days, and 
if the meningococci are found, to inject the 
serum. In cases of sequelae, or recurrence, if 
there is doubt as to the advisability of the use 
of the serum, the question is best decided by 
bacteriologic study of the cerebro-spinal fluid. 
If meningococci are present, the use of the 
serum is indicated; otherwise not. 

If the cases treated by serum are divided into 
two groups, those in which only one dose or 
insufficiently large doses are given, and those 
in which sufficiently large and frequently re- 
peated injections were used, we find the follow- 
ing results: In the first group, 77 eases with 21 
deaths; namely 27 per cent. In the second 
group, 282 cases, with 23 deaths, namely 8.15 
per cent. A comparison of these figures shows 
that it is not sufficient merely to inject the 
serum. It must be injected in sufficient quan- 
tity, and repeatedly, in order to obtain the best 
results from its use. 

Dunn (Boston Md. & Surg. Jour. 1908, clix, 
p. 743) emphasizes the necessity of injecting 
the antimeningitis serum into the subdural 
space and of using sufficient doses. His pres- 
ent practice is to regard 30 c.c. as a minimal 
dose, except in very young infants and in cases 
in which only a small amount of fluid can be 
withdrawn and an obstacle is encountered be- 
fore the entire quantity of serum has been in- 
jected. 



THE HYPODERMIC SYRINGE. 91 

As a rule, the serum passes readily into the 
spinal canal, when injected either by means of 
a syringe or by means of gravity, using a fun- 
nel connected with the needle by a rubber tube. 
In all cases it is essential to remove as much 
cerebro-spinal fluid as possible, as it is desir- 
able to make space for the serum. Free aspira- 
tion presents the advantage of making a form of 
negative pressure in the ventricles which draws 
the serum upwards toward the brain. The 
spreading of the serum into the skull may also 
be favored by placing the patient with the head 
a little low, immediately after completing the 
injection. If more than 30 c.c. of fluid is with- 
drawn, the amount of serum injected may be 
correspondingly increased. In severe and ful- 
minant cases the full dose of 45 c.c. should be 
introduced, unless indications exist to the con- 
trary. 

The effect of a single injection tends to pass 
off in rather more than twenty-four hours, after 
which time the symptoms return. It is best 
however, not to wait for the return of the 
symptoms. The injection should be repeated 
at intervals of twelve to twenty-four hours un- 
til four injections have been given, even though 
the diplococci disappear from the spinal fluid 
and the symptoms clear up. If the organisms 
have not entirely disappeared from the fluid at 
the end of four days, the injections should be 
continued until no more organisms are found. 
In severe and fulminant cases the second injec- 
tion should be given at the end of twelve hours, 



92 THE HYPODERMIC SYRINGE. 

and if there is no improvement a third injection 
should be given at the same interval. The 
treatment of relapses is the same as the treat- 
ment of prolonged cases showing exacerbations 
of symptoms. Lumbar puncture should be per- 
formed immediately, and daily injections of 
full doses of the serum should be given as long 
as a diplococci can be found in the spinal fluid. 
At least four injections should be given at 
twenty-four-hour intervals. 

Finley and White (Montreal Med. Jour., Sept. 
1908) state that the serum used in the treat- 
ment of cerebro-spinal meningitis should be in- 
jected slowly at the rate of 2 c.c. per thirty sec- 
onds. It is advisable to use a general anes- 
thetic during the injection. If there is shock 
following the operation, camphor and strych- 
nine may be injected hypodermically. The 
temperature usually falls after the first two or 
three doses of serum. All of the cases which 
came under treatment before the fifth day of 
the disease recovered. The only death was in a 
case which came under treatment later. If 
mild symptoms, such as a slight elevation of 
temperature, retraction of the head, or Ker- 
nig's sign persist after the bacteria have disap- 
peared from the spinal fluid, a simple puncture 
may sometimes relieve these without the injec- 
tion of serum. 

The gravity method (J. A. M. A. Mar. 23, 
1912, p. 843) of administration is strongly advo- 
cated by some clinicians, who claim that this 
method has many advantages and but few dis- 



THE HYPODEBMIC SYRINGE. 93 

advantages of the syringe method. The after 
effects are usually less severe, the temperature 
lower, the patient feels more comfortable, the 
general condition better when the gravity 
method is employed. 

The serum, after being warmed to body tem- 
perature (care must be exercised not to warm 
the serum beyond 100° F. otherwise it will co- 
agulate) is introduced very slowly. An assistant 
takes the blood pressure readings throughout 
the operations. These readings indicate not 
only the quantity of serum that may be safely 
injected, but also the rate of injection. 

The serum is allowed to run in very slowly 
by gravity, the flow being regulated by raising 
or lowering the syringe containing the serum, 
which admirably serves the purpose of a fun- 
nel. The barrel of the syringe being sterile 
insures a sterile funnel and prevents the dan- 
ger of infecting the serum. The time taken for 
the injection is generally 10 minutes, though 20 
or more minutes may be taken, especially in 
cases beginning with low blood-pressure, or 
when the blood-pressure drops very quickly. 
The blood pressure lessens continuously from 
the beginning of the injection. 

The barrel of the syringe containing the se- 
rum is attached to 10 or 12 inches of rubber 
tubing about *4 inch in diameter. With the 
average blood-pressure of 110 or 120 mm. of 
mercury, a total drop of 20 mm. in an adult is 
a safe indication to stop the injection. After 
a fall of 20 to 30 mm. it becomes relatively 



94 THE HYPODERMIC SYRINGE. 

much greater if injection is continued (e. g., 40 
mm. more making a total of 60 mm. or more). 
An instance is mentioned in which this occur- 
red — a few minutes later the patient's heart and 
breathing stopped, though response to imme- 
diate active treatment was prompt. Occasion- 
ally an initial rise is followed by fall as the 
injection is continued. Very rarely a material 
rise occurs after injection. 

The treatment of severe symptoms consists 
in cessation of the injection upon a consider- 
able fall; removal of fluid from the canal at 
once upon a sudden marked fall, by simply 
lowering the syringe-funnel; in grave cases ar- 
tificial respiration; as adjuvants, epinephrin in- 
tramuscularly in large doses, other vascular 
stimulants and atropin. Immediate active treat- 
ment generally provokes response. 

The average dose by the gravity method is 
20 to 25 c.c. in adults; in children in proportion. 
Infants that cannot tolerate more than 2 to 4 
c.c. respond remarkably well. When the blood 
pressure allows, from 30 to 40 c.c. may be in- 
jected, rarely more. 

Clinical Reports. — In the original Working 
Bulletin No. 8, and the revised edition thereof 
of September, 1912, are the following clinical 
reports which are quoted : 

Flexner (J. A. M. A., 1909, ii, p. 560) reports 
the results which had been obtained up to 
November, 1909, in the serum treatment of cere- 
brospinal meningitis. He states that the re- 
ports have come from the pandemic of 1904-08. 



THE HYPODERMIC SYRINGE. 95 

The results obtained in the United States are not 
so conclusive as those obtained in Europe, be- 
cause in this country the epidemic had already 
passed its height when serum treatment was 
first used, whereas in Europe it was still rag- 
ing with full virulence. In Germany the epi- 
demic was virtually at an end when serum 
treatment was instituted. In France, on the 
other hand, the serum was available at the be- 
ginning of the outbreak. The Rockefeller In- 
stitute sent supplies to Professors Calmette, 
Netter and Roux. The reports of the serum 
treatment now appearing in the French medical 
Journals are based chiefly on the use of the 
serum prepared at the Rockefeller Institute. 

In France the mortality of cases treated with 
serum has been less than 25 per cent., while in 
cases treated without the serum it has aver- 
aged 80 per cent. The results obtained in this 
country and in England were quite similar. We 
have statistics of 712 cases in w T hich a bacterio- 
logic diagnosis was made. In these cases the 
total mortality was 31.4 per cent. In infants 
less than two years old the mortality was 42.3 
per cent. In previous epidemics it has general- 
ly averaged upwards of 90 per cent. In cases 
where the injections were given within the first 
three days of the disease the mortality of in- 
fants less than two years old was only 5.8 per 
cent. There was no such striking difference 
between the results obtained by earlier injec- 
tions in older persons. The total mortality of 
the cases injected before the seventh day was 



96 THE HYPODERMIC SYRINGE. 

26 per cent., and among those who received 
their first injection after the seventh day of the 
disease, it was 42 per cent. 

During an epidemic the existence of the dis- 
ease will often be suspected before meningeal 
symptoms are apparent. In such cases the di- 
agnosis may be made by examination of the 
spinal fluid, which will usually be turbid and 
will always show the presence of meningococci. 
If the serum is injected immediately, such cases 
are almost always terminated or run a mild 
course. 

Flexner (J. A. M. A., Vol. i, No. 25), in a 
paper read before the American Medical Asso- 
ciation, states that more than 1000 cases of epi- 
demic meningitis, diagnosed bacteriologically, 
have been treated with his serum. The serum 
is obtained by immunizing horses, first by 
means of dead and then by means of living cul- 
tures of meningococci, first injected subcutane- 
ously and then into the veins. Of these cases 
550 have been carefully analyzed and it is 
found that in Scotland and Ireland the mortal- 
ity had apparently been reduced from 75 per 
cent, to less than 30 per cent. In Edinburgh 
the mortality had boon reduced to about 40 per 
cent., and in Belfast to less than 30 per cent. 
In this country and France the results were 
much the same. 

Abbott, in discussing this paper, said that 
his experience in Philadelphia had been very 
favorable. Twenty patients were treated with 



THE HYPODERMIC SYRINGE. 97 

the serum and the results were better than any 
other treatment ever tried. 

Koplik stated that the results had been es- 
pecially gratifying in children under two years 
of age. Up to that time he had treated six 
babies, from five months to two years old, with 
three complete recoveries. 

Ewing remarked that a series of cases should 
be treated with injections of normal horse se- 
rum and the results compared with results from 
meningitis serum. 

Dr. Flexner replied that he did not think it 
would be justifiable to carry out such an ex- 
periment on human beings, but that such a 
comparison had been made with monkeys, and 
the results obtained by the use of the menin- 
gococci serum were much better than those ob- 
tained by injections of normal horse serum. 

In the Archives of Pedriatics, 1908, page 747, 
Flexner and Jobling report 393 cases of epi- 
demic meningitis treated with serum. The 
cases have arisen in different and widely separ- 
ated parts of the United States, Canada and 
Great Britain. Bacteriologic diagnosis was 
made in every case. Cases in which death oc- 
curred within twenty-four hours of the time of 
injection have been excluded from the sum- 
mary, as it has been shown that the beneficial 
effects of the serum are not exerted until after 
this period. Of these 393 cases 295, or 75 per 
cent, recovered. The mortality of cases in 
which the first injection was given from the 
first to the third day of the disease was 16 per 



98 THE HYPODERMIC SYRINGE. 

cent; from the fourth to the seventh day, 24 
per cent and later than the seventh day, 35 
per cent. About 75 per cent of the cases treat 
ed with serum terminated by crisis. Relapses 
have not been frequent and fatal termination 
has been exceptional when the serum treatment 
has been resumed. The only sequel which was 
reported was deafness, which was seen in only 
a few cases. 

Churchill (Arch, of Ped., p. 754) reports nine 
cases of meningitis in which the meningococcus 
was found, which were treated with the Flex- 
ner serum. Seven of these cases recovered, all 
without serious sequelae. The first effect noted 
clinically was the change in the patients' men- 
tality. They seemed brighter and more ration- 
al after the first, second and third doses of the 
serum, as the case might be and this improve- 
ment continued steadily until the patient was 
well. It was a curious sight to see a patient 
with the head markedly retracted, yet perfectly 
quiet and without pain, interested in his sur- 
roundings. The temperature fell almost at the 
same time that the mental improvement began, 
and the leucocytosis diminished. Examination 
of the first specimen of spinal fluid obtained by 
spinal puncture generally showed large num- 
bers of leucocytes and also meningococci, vary- 
ing in numbers with the intensity of the disease. 
Subcutaneous punctures showed a fluid less 
cloudy, and containing fewer cells and organ- 
isms. Churchill believes that in a case of sus- 
pected meningitis it is our duty to do a lumbar 



THE HYPODERMIC SYRINGE. 99 

puncture, and if we obtain a cloudy fluid to in- 
ject at once into the spinal canal, subsequent in- 
jections being determined by the results of the 
bacteriological examinations of the spinal fluid. 
If this shows the presence of meningococci the 
serum should be repeated every day for three 
or four days, as necessary. 

Dunn (Arch, of Ped. p. 756) reports 40 cases 
of cerebro-spinal meningitis treated with the 
Plexner serum. All the cases in which the dip- 
lococeus intracellularis was found are included 
in the series. The serum was administered into 
the spinal canal, as recommended by Dr. Flex- 
ner. If the fluid obtained by puncture was 
clear no serum was given unless the bacterio 
logic examination showed the presence of the 
diplococcus. But if the fluid was cloudy the 
serum was injected at once. The routine dose 
was 30 c.c, the maximum dose 45 c.c. If the 
amount of fluid obtained by puncture was small 
and increase of intradural pressure was feared, 
amounts as small as 10 c.c. were often injected. 
Thirty-one of the 40 cases recovered, one being 
deaf and one deaf and blind. The lowest mor- 
tality in any previous year was 58 per cent 
varying between this and 80 per cent. The 
mortality in the year referred to by Dunn was 
only 19 per cent, under the use of the Flexner 
serum. Of the nine fatal cases in the series, 
five were seen quite late in the course of the 
disease, and in one case the serum was not 
given until the patient was actually moribund. 
Of the other four fatal cases one was of the 



100 THE HYPODERMIC SYRINGE. 

fulminating type, one very severe, and one died 
of intercurrent broncho-pneumonia which came 
on after the temperature had returned to nor- 
mal and the meningeal symptoms had sub- 
sided. The fourth case was one of normal 
severity, in which the serum appeared to pro- 
duce the improvement in the beginning, but 
which was later uninfluenced by the treat- 
ment. The most noticeable effect of the treat- 
ment is not its influence on the mortality, but 
the remarkable improvement which takes place 
in individual cases after the injection of serum. 
It produces first a fall in temperature; sec- 
ond, a rapid improvement in the patient's gen- 
eral condition, and, third, a shortening of the 
course of the disease. The first injection of 
serum is often followed by a critical fall, which 
is sometimes permanent. In other cases the 
temperature returns to a high point and falls 
by lysis. The effect on the general condition 
of the patient is most striking. There is a 
permanent return to consciousness and disap- 
pearance of delirium and headache as well as 
hyperesthesia and vomiting. These symptoms 
are often completely relieved within twenty- 
four hours after the first injection, the patient 
changing in the most remarkable way from a 
condition of coma to a condition of normal 
mentality and activity. The average length of 
time patients remained under treatment was 
but a small fraction of the time patients who 
recovered remained under treatment in previ- 
ous years. Another marked effect of the serum 



THE HYPODERMIC SYRINGE. 101 

is as regards the character of the spinal fluid. 
The fluid first withdrawn is turbid and shows 
large numbers of leucocytes and diplococci. 
Twenty-four hours after the first injection the 
number of organisms is much smaller and the 
majority are intracellular, only rare extracellu- 
lar forms being seen. The third lumbar punc- 
ture shows still fewer diplococci, and only in- 
tracellular forms. After the third injection it 
is unusual to find any diplococci. Relapses 
sometimes occur under the use of the serum, 
but these usually yield to repeated doses. 

Although the serum is ordinarily without 
benefit in chronic cases, it may occasionally do 
good. One patient in the late chronic stage 
began to improve immediately after the first 
injection and made a rapid convalescence. 
There is always some hope of a good result as 
long as diplococci are present. The serum 
causes a cessation of the active process in most 
cases and the result of the disease depends 
mainly on the extent of tissue damage which 
has already been done. The value of this 
serum is comparable to that of diphtheria anti- 
toxin. 

Knox and Sladen (Arch, of Ped. p. 761) re- 
port 21 cases treated with Flexner serum in 
Johns Hopkins Hospital; three of these cases 
died, a mortality of 14 per cent. The effect of 
the first injection was usually a rapid fall in 
temperature. In one case this remained nor- 
mal, but ordinarily there was a rise the next 
day and at least three injections were required 



102 THE HYPODERMIC SYRINGE. 

to induce permanent low temperature. From 
three to twelve hours after the injection the 
headache, delirium, and pain in the back be- 
gan to disappear. Stiffness of the neck and 
Kernig's sign were more persistent. Pressure 
symptoms were often relieved by the treatment, 
although fluid obtained by puncture was al- 
ways replaced by at least an equal quantity 
of serum. The effect on the spinal fluid was 
the same as reported by other authors. It 
seems probable that the serum has both an 
antitoxic and bactericidal power. 

In discussing the above papers Dr. Koplik 
stated that he had treated 13 cases with serum, 
there being two deaths, both infants less than 
one year old. 

In the discussion Dr. Wilkinson stated that 
he had treated 10 cases at the Garfield Hospital 
in Washington, with seven recoveries. Of the 
three that died, one had marked hydrocepha- 
lus, and one might possibly have been cured 
if larger doses had been given. The third case 
was in a comatose condition when the treat- 
ment was begun. There was considerable im- 
provement in the meningeal symptoms and in 
the spinal fluid after the injection of the serum, 
but intestinal paralysis developed and the case 
ended fatally. The best results have been ob- 
tained with injections of from 15 to 30 c.c. The 
symptoms generally subsided in four or five 
days, the organisms at the same time disap- 
pearing from the spinal fluid. 



THE HYPODEKMIC SYRINGE. 103 

In closing the discussion Dr. Flexner re- 
ported statistics from Belfast. During the 
height of the epidemic, a mortality of 75 per 
cent, was reported, although in the hospitals 
where the serum treatment was being used the 
mortality was only 26 per cent. The serum 
belongs to the class of bacteriolytic sera, in 
the preparation of which we are obliged to 
use the entire constituents of the organisms. 
We have three antitoxic bacteriolytic sera, 
diphtheria, tetanus and dysentery. The pe- 
culiarity of these sera is that any dose of the 
corresponding toxin may be neutralized if a 
sufficient amount of the serum is given. The 
antimeningitis serum, on the other hand, does 
not produce neutralization of the toxin accord- 
ing to the law of multiples. The dose of toxin 
can be made so great that the serum becomes 
ineffective. The important point in the ad- 
ministration of the serum is that it shall be 
given in sufficient concentration and directly 
into the spinal canal. If given into the circula- 
tion the secretion into the subdural space is 
slow and imperfect. 

Chase and Hunt (Arch, of Int. Med. 1908. 
iii, p. 294) report an epidemic of cerebrospinal 
meningitis in Akron, Ohio, in which the Flex- 
ner serum was used. Twenty-two cases were 
seen. In 12 of these the serum treatment was 
used, with three deaths, a mortality of 25 per 
cent. In 10 cases the serum was not used, and 
nine of the patients died, a mortality of 90 
per cent. The diagnosis was made in each case 



104 THE HYPODERMIC SYRINGE. 

by the finding of the diplococcus of Weichsel- 
baum. The only medication any of the patients 
received aside from the injections of serum 
was an occasional hypodermic injection of 
morphine combined with hyoscine, when deliri- 
um and restlessness were pronounced. The 12 
cases treated with serum are reported in detail. 
The authors ascribe the low mortality of the 
series to the use of the serum, as there was 
no other difference between these cases and 
the 10 cases previously mentioned. 

Koplik (Med. Rec/l908, ii, p. 557) reports 
13 cases treated with serum. The punctures 
were carried out in the median line and the 
serum introduced, not with a syringe but with 
a funnel. A glass funnel holding about 20 
c.c. is the best. The pressure exerted by the 
syringe is likely to be dangerous. Two patients 
were less than six months old, and in each 
case the disease had been in existence for sev- 
eral weeks. Both died. The 11 other cases 
recovered. The previous mortality had never 
been less than 40 per cent. 

Ladd (Med. Rec. 1909, i, p. 1,055), in a paper 
read before the American Medical Associa- 
tion, states that the serum treatment was used 
in an epidemic of cerebrospinal meningitis in 
Ohio, in which the mortality had previously 
been 80 per cent. The serum was used in 31 
cases, with 20 recoveries; a mortality of 35.5 
per cent. All of the cases treated on the first 
day of the disease recovered. 

Rotch (J. A. M. A. 1909, Oct. 30, p. 1,443) 



THE HYPODERMIC SYRINGE. 105 

of Boston stated that from November 1, 1907, 
to November 1, 1908, antimeningococcus serum 
was employed at the Children's Hospital, Bos- 
ton, with the result that the mortality from ce- 
rebrospinal meningitis immediately fell from 80 
per cent, to 19 per cent., and that it never 
went over 25 per cent., while before the em- 
ployment of the serum the mortality had been 
from 60 to 80 per cent. 

In addition to improved statistics of mortal- 
ity, the conditions of the patients surviving 
were wonderfully improved. The terrible 
sequels — hydrocephalus, mental and physical 
deteriorations, blindness, deafness, paralysis — 
rarely ensue in cases treated with serum. Then, 
too, the duration of the disease has been 
markedly shortened, the old persistence for 
weeks and months being infrequent under the 
new treatment. 

Past Asst. Surgeon E. H. von Ezdorf found, 
in the recent epidemic in Texas (1911-1912) 
that of 410 healthy persons who had been ex- 
posed to the disease, 59.6 per cent, were car- 
riers of the meningococcus, and, from cultures, 
53.75 positive carriers. 

Dr. A. W. Nash, of the City Hospital of 
Dallas, Texas, states that experience gained 
in the recent epidemic of cerebrospinal men- 
ingitis in Texas has demonstrated that better 
results may be obtained by withdrawing from 
the cord not all of the spinal liquid that can 
be removed, but only that sufficient to re- 
lieve the pressure; furthermore, instead of in- 



106 THE HYPODERMIC SYRINGE. 

jecting sufficient antimeningitis serum to re- 
place the amount of liquid removed, better re- 
sults are secured when one-half as much serum 
is used as liquid withdrawn. That is to say, 
if 30 c.c. of spinal liquid are withdrawn, from 
15 to 20 c.c. should be employed. 

Up to January 27, 1912, reports of the State 
Health Officer listed a total of 550 cases and 
210 deaths occurring in 49 counties of the state. 
In Oklahoma, in this epidemic as reported from 
December 1, 1911, to January 25, 1912, there 
were 72 developed cases and 2 suspects, with 
a total of 36 deaths in 14 counties. The spinal 
fluid was microscopically examined. Antimen- 
ingitis serum was used with the result that the 
mortality was reduced to 10 per cent. With 
out the serum the mortality was from 75 to 90 
per cent. 

Dopter (Ann. de Tlnst. Pasteur, xxvi, 1910, 
p. 96) reports that of 402 patients treated with 
the serum, 66 died — a mortality of 16.44 per 
cent. The author believes there is a danger in 
doses given in excess of 50 c.c. during 24 hours 
or if more than three injections are made in 
24 hours. 

Langfeld (West. Med. Rev. Apr. 1912, p. 
201) reports 5 cases of cerebrospinal mening- 
itis in which antimeningitis serum was used, 
with 5 recoveries ; 4 patients were treated in a 
hospital and 1 at home. He withdrew as high 
as 60 c.c. of cerebrospinal fluid from one adult, 
replacing this by 60 c.c. of serum. During the 
first 24 hours 2 injections were given in all 



THE HYPODERMIC SYRINGE. 107 

except the mildest cases. Langfeld believes 
it is best always to give an anesthetic, and 
daily injections after the second until the 
specific diplococcus is no longer demonstrable 
by microscopic examination of the cerebro- 
spinal fluid. Lumbar puncture is a harmless 
procedure, not difficult to perform, and should 
the cerebrospinal fluid withdrawn not be as 
clear as water, 30 to 45 c.c. of antimeningitis 
serum should be introduced, as no harm will 
result than from the subcutaneous injection of 
diphtheria antitoxin. 

In the first case, a female patient, aged 22, 
the effect of the first injection was magical; 
from 2 to 4 hours afterwards the patient re- 
gained consciousness and called to the nurse 
for water and then for milk. In all, 220 c.c. 
were withdrawn and 225 c.c. of antimeningitis 
serum administered. In the third (a male of 
14), 280 c.c. were withdrawn and 295 c.c. ad- 
ministered. In the fourth (female, age 4), 256 
and 275, and in the fifth (female, age 11) 210 
and 225. 

Langfeld concludes: 

1. While admitting the existence of ful- 
minating cases, a large proportion have pro- 
dromal symptoms from 2 to 6 days before 
acute symptoms, during which state a positive 
diagnosis is possible by means of spinal punc- 
ture and microscopic examination of the cere- 
brospinal fluid. 

2. That there is no danger in lumbar punc- 
ture. 



108 THE HYPODERMIC SYRINGE. 

. 3. That the antimeningitis serum is a spec- 
ific for that form of cerebrospinal fever due 
to the diplococcus intracellulars meningitidis. 
Its action is immediate, bringing about: 

(a) Rapid restoration to consciousness from 
delirium and mania. 

(b) Equally rapid reduction in tempera- 
ture, especially if this is very high. 

(c) Miraculous disappearance of pain in 
the head and back; no other drugs required. 

(d) Cessation of vomiting. 

(e) Direct action on cerebrospinal fluid ; 
which is quickly made to resume normal con- 
dition. 

(f) Only by its use is there prevention of 
such sequels as deafness, blindness, etc. 

4. That in injecting the serum the quantity 
introduced may be made greater than that 
withdrawn, if care is taken not to use too 
great force in its introduction. 

Herold (J. A. M. A. Aug. 10, 1912, pp. 444- 
445) reports an extremely grave case of epi- 
demic cerebrospinal meningitis in which the 
injection of 420 c.c. of serum brought about 
recovery. The patient, a school boy of 17, 
showed undoubted evidences of epidemic cere- 
brospinal meningitis, including rigidity of the 
neck, Kernig's sign and partial delirium. The 
case was an extremely grave one and twice the 
patient was considered "in extremis," when 
oxygen was administered. Thirty c.c. doses 
of serum were administered each day from the 
1st to the 7th, except the 4th, when the patient 



THE HYPODERMIC SYRINGE. 109 

was thought to be in extremis. On the 8th day 
60 c.e. were administered, followed in the next 
30 hours by 180 c.c. in 3 doses, or 420 c.c. in 
all. One month after the onset of the disease 
the patient was discharged as cured. Herold 
believes that complete recovery would not have 
occurred had he stopped on the 8th day with 
240 c.c. 

CAUSES OF FAILURE. 

In a certain percentage of cases the serum 
has seemingly failed without apparent reason. 
In discussing this question, the Journal of the 
American Medical Association, 1911, ii, p. 823, 
suggests the possible reasons for such failures: 

"It is possible that the cause of failure to 
obtain good results from the use of antimen- 
ingitis serum sometimes experienced may be 
due either to an obstruction to the passage of 
the fluid, by a plug or pus, etc., so that the 
serum cannot reach certain parts of the brain 
infected, or to the fact that there are present 
strains of the diplococcus intracellularis other 
than the one employed in the preparation of 
the serum. For this reason preference should 
be given to a polyvalent serum, i.e., one ob- 
tained from horses immunized with many 
strains of the diplococcus intracellularis. " 

As has been cited by some authors, it is pos- 
sible that some failures are due to the fact that 
the focus of infection is so located as not to 
be reached by injections within the spinal 
canal. Such instances have been mentioned in 
preceding pages. 



110 THE HYPODERMIC SYRINGE. 

AUXILIARY TREATMENT. 

While the serum is a specific remedy, there 
are frequently indications for other therapeutic 
agents, and discussing the therapeutics of cere- 
brospinal meningitis, the Journal of the Amer- 
ican Medical Association, 1911, ii, p. 823, gives 
the outlines of the auxiliary medical treatment 
as follows: 

Nose, throat and eyes, too, if there is con- 
junctivitis, must be kept clean with antiseptics 
— for the throat a spray or gargle such as 
warm hydrogen peroxide solution (1:5); for 
the nose, a warm weak alkaline solution, e.g., 
diluted liquor antisepticus alkalinus; for the 
eyes, boric acid solution. The position of the 
body and limbs should be that which gives 
least pain and most comfort ; painful joints 
should be wrapped with cotton. 

Calomel, followed by a gentle saline, should 
be given. The patient should receive plenty 
of water, but food is best withheld for a day 
or two, especially if vomiting and anorexia are 
present. After that the simplest foods in small 
amounts, of which the best are milk, oat-meal 
gruel, egg-albumin, and, later on, meat-juice 
at three hour intervals, are advised. Persistent 
vomiting and intense nausea require hypoder- 
mics of morphine, the dose and frequency 
varying with the intensity and age of the 
child. To ensure sleep, muscle-relaxation and 
nerve rest-essential in the treatment of men- 
ingitis — chloral or bromides are indicated. 



THE HYPODERMIC SYRINGE. Ill 

For relief of inflammation, ergot intramus- 
cularly into the deltoid, or calves of the legs 
if it is repeated frequently. This drug is con- 
traindicated only in excessive heart-action and 
high blood-pressure, in which condition nitro- 
glycerine, or, preferably, blood-letting will give 
relief. A child of 10 should receive half the adult 
dose of ergot, which is a hypodermic syringe- 
ful of 1 c.c. (15 minims) of a good aseptic 
ergot. A child of 5, one-half of this dose or 
7% minims; or a proportionate part may be 
given of the more concentrated form in an 
aseptic ampul. In 3 hours, if there is no im- 
provement, the dose is repeated, and then once 
in 6 hours, until there is a decided action. In 
addition to its sedative action on the nervous 
system, ergot aids and prolongs the action of 
the morphine, thus diminishing the dose or 
curtailing the use of the latter. Only reliable 
ergot should be used under strictly aseptic 
conditions. A wet dressing of alcohol in warm 
water (1:3 or 1:4) will relieve temporary pain 
and swelling at the site of the injection. 

Ice applied to the head and spine is bene- 
ficial, or in some instances hot sponge-baths 
are preferable for relieving internal congestion. 

Alcohol and nervous excitants, such as 
strychnine, caffeine and quinine are contrain- 
dicated. 

In prolonged coma from pressure, lumbar 
puncture should be made. 

The general care of the patient is the same 
as in any grave illness — a large, quiet, well- 



112 THE HYPODERMIC SYRINGE. 

ventilated room affording access to sunlight, 
the patient's eyes being shaded or screened, the 
feet kept warm, the bowels kept open. 

As recovery sets in, ergot is discontinued and 
sodium iodide, in small doses for absorption 
of exudates, is given 3 times a day, the dose 
for a child of 5 being not more than 2 grains 
(0.10 gm.). Iron, in small doses, probably 
combined with a bitter tonic, is indicated in 
convalescence. 

The patient should remain in bed at least 
a week after cessation of active symptoms, and 
should postpone resuming his duties as long 
as possible. Massage and electricity, at first 
mild, should be applied to affected joints and 
muscles. Joint-adhesions should be broken up 
under chloroform anesthesia. 

Normal Serum — The normal serum of the 
blood has been found of use in the treatment 
of hemophilia and hemorrhages due to other 
causes, and has come quite extensively into 
use. It is administed both orally and hypoder- 
mically, and consequently has a place in these 
pagres. In Working Bulletin Xo. 13, November, 
1911, in which Normal Serum is given elaborate 
discussion, as are the conditions in which it is 
applicable, is found the following data : 

SYNOPSIS. 

Normal Serum is that obtained from the 
blood of normal horses, as distinguished from 
that obtained from horses undergoing the pro- 
cess of immunization for the production of 



THE HYPODERMIC SYRINGE. 113 

curative serum. It has, of late years, come 
extensively into use as a remedy for hemo- 
philia and other forms of hemorrhage, i.e., 
hemorrhages from wounds and fractures or 
following surgical operations. While serum 
from various animals (horse, rabbit, sheep) has 
been employed, that from the horse is generally 
used. The same care in selecting healthy an- 
imals and in preparing the serum should be 
taken as is employed in the production of diph- 
theria antitoxin. 

Normal serum is used hypodermically in 
hemophilia in doses of from 20 to 30 cc, or 
intravenously in doses of from 10 to 20 cc, to 
be repeated, if necessary, after an interval of 
two days. 

The dosage by the mouth is from 30 to 80 
cc, in divided portions during 24 hours. 

As a preventive of hemorrhage during and 
after surgical operations, 20 cc. may be in- 
jected the day after operation. 

Local applications on saturated cotton may 
be freely made to oozing surfaces. The tech- 
nique for hypodermic use is the same as that 
for injecting curative serums. 

ETIOLOGY AND PATHOLOGY OP HEMO- 
PHILIA. 

Hemophilia, or hemorrhagic diathesis, means 
a tendency to profuse or even uncontrollable 
hemorrhage, occurring spontaneously or as a 
result of a trivial injury. The hemorrhage 
may take place from mucous or serous mem- 



114 THE HYPODERMIC SYEINGE. 

branes, or from wounds of the skin. The blood 
may escape into the tissues, into organs, or 
under the scalp, or into the external genitals. 
If a cut is made the hemorrhage from the 
larger vessels is easily arrested, but capillary 
oozing continues, so that a child who is a 
11 bleeder" must be unceasingly watched and 
guarded. 

The hemorrhagic diathesis is far more com- 
mon in men. Its existence is rarely suspected 
until after the first dentition and possibly not 
until puberty. According to R. C. Cabet, in 
70 per cent, of cases it appears before the fifth 
year. 

The disease is transmitted by heredity. It 
may descend to the off-spring of the mother, 
who is usually free from the disease but whose 
father was subject to it. It may not be sus- 
pected until the extraction of a tooth or some 
trivial accident, is followed by persistent 
bleeding. 

The cause of hemophilia is still undergoing 
investigation. It has been assumed that there 
is a condition of the blood which prevents 
coagulation, but according to Da Costa's 
"Modern Surgery," the blood of the hemo- 
philic coagulates outside the body as well as 
anv other blood. 

Emile Weil (Le Bui. Med. Oct. 16, 1907^, 
and Dejardin (Internat. Med. Ann. 1909; Br. 
Med. Jour. Dec. 12, 1908) agree in regard to 
the pathology of hemophilia. It is pointed out 
that the coagulation and formation of fibrin 



THE HYPODERMIC SYRINGE. 115 

are due to the action of a ferment contained 
in the leucocytes on an albuminoid substance, 
held in solution by the plasma of the blood. 
These authors hold that in milder forms of 
hemophilia, the failure of coagulation, to which 
the symptoms are due, is caused solely by in- 
sufficiency or imperfection of the ferment, 
while in the more severe and inherited form, 
faulty condition of the ferment is associated 
with the presence in the blood of anticoagulable 
material. Some maintain that there is a struc- 
tural defect in the capillaries, but in a case 
of hemophilia in the Jefferson Medical College 
Hospital, in which it was absolutely necessary 
to amputate a finger because of a crush, a 
careful study of the vessels of the fingers by 
Dr. Copeland, failed to show any disease of the 
blood-vessels. 

A suggestive editorial, " Serum Injections in 
Hemophilia,'' in the Medical Record, Aug. 8, 
1908, p. 239, states: "In the greater majority 
of cases hemophilia is a hereditary constitu- 
tional fault; at times, however, it is acquired. 
The symptoms of both varieties are similar and 
well known, and in both the coagulation time 
of the blood is much retarded. In a recent 
issue of the Revue Pratique d'Obstetrique et de 
Pediatrie, P. E. Weil differentiates between 
the accidental, transitory and congenital vari- 
ety: In the former, he found the blood to be 
thin and to flow rapidly through a needle in- 
serted into a vein; the leucocyte count was 
normal, and the coagulation time was seventy- 



116 THE HYPODERMIC SYEINGE. 

five minutes, the coagulum being solid and the 
serum plentiful. In the congenital variety the 
blood was sticky and flowed slowly; there was 
an increase in the percentage of uninuclear 
leucocytes, and the coagulation times was from 
two to nine hours, the coagulum being soft and 
the quantity of serum small. Weil found that 
when three minims of animal serum were added 
to three cubic centimetres of blood taken from 
a patient suffering from either variety of hemo- 
philia, coagulation occurred in five to ten 
minutes. When he injected 10 to 20 c.c. of 
normal blood intravenously, or 20 to 30 sub- 
cutaneously into these patients, he found that 
the coagulation time was practically normal 
two days after injection, and remained so sev- 
eral weeks, this effect being a little less marked 
in the congenital variety. He also found that 
normal serum applied locally had a styptic ac- 
tion. Weil therefore, advises the injection of 
normal serum, or, if it cannot be had, diph- 
theria antitoxin, for the bleeding in hemophilic 
patients in whom styptics, compresses, ergot, 
ice, calcium lactate, gelatin, etc., have been un- 
successful." 

In the cases of hemophilia neonatorum re- 
ported by J. E. Welch (Am. Jour, of Med. Sci. 
June, 1910), the bleeding appeared as a rule 
during the first week of life, and it occurred 
very frequently on the second, third and fourth 
days. 

The primary bleeding, as stated by the 
author, may be entirely in the skin or mucous 



THE HYPODERMIC SYRINGE, 117 

membrane surfaces. On postmortem he found 
that the principal hemorrhage may be in the 
brain (with extensive laceration) or in the 
liver, in which case the capsule may be entirely 
dissected from the surface of the organ ; and in 
addition to these, hemorrhagic spots in other 
internal organs and effusions of blood in the 
various serous cavities were found, and in some 
instances he found the spinal canal filled with 
blood. 

As the author states, the first bleeding may 
be a slight oozing from the umbilical cord at 
its point of junction with the skin surface, and 
not from the end of the cord due to faulty 
tying. This cord hemorrhage may persist in 
spite of all local remedies, and in the course 
of two or three days a considerable quantity 
of blood may be lost by this apparently insig- 
nificant bleeding, Other bleeding may come 
from the gastro-intestinal tract, as evidenced 
by the vomiting of blood or bleeding from the 
rectum. The lips and gums also frequently 
bleed. Often the severest hemorrhage appears 
in the skin; and, as a result, large hematomas 
(blood tumors) may form bearing no relation 
whatever to traumatism. 

Agnew (Da Costa's "Modern Surgery"), re- 
ported a case in which hemophilia was limited 
to the head and neck and there have been cases 
in which the bleeding occurred from one kid- 
ney. 

Hahn (Med. Rec. Oct. 8, 1910, p. 624) states 
that, "Of all the theories concerning the causa- 



118 THE HYPODERMIC SYE1NGE. 

tion of hemophilia, the most tenable seems to 
be the one formulated by Sahli — that there 
is a chemical change in the walls of the blood- 
vessels. Normally, when the blood-vessels are 
cut, a substance is secreted by the vessel-walls 
which causes clotting of the blood and conse- 
quent closure of the mouths of the bleeding 
vessels. But in hemophilia, according to Sahli, 
this secretion is wanting, thus explaining the 
fact that hemophilic individuals continue to 
bleed, although the coagulation time of the 
same blood outside the body may not be in- 
creased. On the basis of this hypothesis, it 
seems rational to attempt to supply the missing 
substance by the use of normal serum. This 
principle in the treatment of the disease is not 
new. Normal serum has been used in these 
cases in various ways. It has been given by 
mouth, subcutaneously and by injection into 
the bleeding area. " 

THE ACTION OF NORMAL SERUM IN 
HEMOPHILIA. 

In discussing the means of preventing hem- 
orrhage in hemophilia and also of protecting 
those about to undergo surgical operation, 
Dejardin (Internat. Med. Ann. 1909; Br. Med. 
Jour. Dec. 12, 1908) quoted Weil as stating 
that serum, when added in a dose of three 
drops to three c.c. of blood of a hemophilic 
subject, favors coagulation to a marked degree 
in the inherited form and also in the accidental 
form of the disease. The subcutaneous or, 



THE HYPODEEMIC SYKINGE. 119 

preferably, intravenous injection of fresh 
serum in the subject of the latter form of the 
disease will be speedily followed by normal 
coagulability of the blood, and this will per- 
sist for about a month. In cases of inherited 
hemophilia, such injection, though not acting 
so completely, will favorably modify the 
anomalies of coagulation. 

CLINICAL USE OF NORMAL SERUM. 

Wirth ("Wein. klin. Woch. 1909, No. 3) has 
had considerable experience with this treat- 
ment, which he reports in detail. In one 
patient, a boy of 14, known to be a hemophiliac, 
a persisting hemorrhage from the nose, throat 
and gums was stopped under application of 
diphtheria antitoxin locally and injections of 
from 15 to 20 c.c. No ill effects were observed 
and the hemorrhagic tendency was kept under 
complete control for six months. In another 
case, a hemophilic girl of 15 with metrorrhagia 
and epistaxis was injected with horse serum, 
and the uterus and vagina were tampened with 
gauze dipped in normal serum; prompt bene- 
fit followed. 

He has treated 23 patients with hemorrhage 
from various causes, and is now convinced that 
the injections of serum are actually an efficient 
means for treatment. The method is indicated 
in all affections in which the coagulating power 
of the blood is reduced, although it may prove 
effectual in other forms of hemorrhage. 



120 THE HYPODERMIC SYEINGE. 

As a rule, 20 c.c. of serum is enough, but 40 
c.c. may be injected without harm. The sub- 
cutaneous route should be preferred unless the 
intravenous is urgently required. Normal 
serum seems preferable, but antitoxic serum 
may also be applied locally. 

Wirth calls special attention to the subsidence 
of hemorrhages from the skin and mucous 
membrane in a case of cholemia in advanced 
cirrhosis of the liver. One new-born infant, 
bleeding freely from nose and mouth, was 
treated by local application of sponges dipped 
in normal serum and the hemorrhage was soon 
under control. In certain cases of hemorrhages 
of the lower bowel were arrested by injection 
of 10 c.c. of normal serum into the bowel. 

Emile Weil (Le Bui. Med. Oct. 16, 1907), 
in a discussion on hemophilia, states that the 
injection of normal blood serum had given him 
uniform success in all cases used as a preven- 
tive measure in operations and as a curative 
means to stop bleeding. Seven cases were of 
spontaneous hemophilia, four having a strong 
family tendency. The effects of the serum 
were shown in from twelve to twenty-four 
hours after subcutaneous or intravenous injec- 
tion, and lasted for a period of one to two 
months. Weil says that normal serum exer- 
cises a local action in controlling external hem- 
orrhage. 

Baum (Mitteil. A. D. Grenzeb. D. Ned. U. 
Chir. 1909, xx, 1-20; Muen. med. Wehn. 1909, 
pp. 56, 834) showed that the addition of fresh 



THE HYPODERMIC SYRINGE. 121 

serum, partly deprived of its coagulating 
power by " hirudin, " hastened the clotting in 
each case "in vitro, " but when it had complete- 
ly lost the coagulating power the addition of 
serum did not restore such power. 

Welch (Am. Jour. Med. Sci. June, 1910), 
having in mind the almost uniform failure of 
drugs in hemophilia, decided to attempt the 
use of normal serum. His first subject was 
three or four days old. The case was thought 
to be hopeless by the attending surgeon, who 
requested his house surgeon to ask permission 
of the parents for a post-mortem examination. 
It was at this time the author made the first 
injection. Ten c.c. were administered sub- 
cutaneously three times during the first day, 
and once each on the following two days. 
Within a few hours a decided improvement 
was noted in the condition of the baby; the 
hemorrhages ceased, and strength returned to 
the child in a very noticeable way. Within 
three days it was quite evident that the child 
was out of danger. The child left the hospital 
in due time without any signs of having been 
a bleeding baby. 

Encouraged by this result, the attending phy- 
sicians of the New York lying-in Hospital, 
placed at the author's disposal for treatment 
all the bleeding babies that appeared in their 
wards. Twelve cases were successfully treated, 
and the author reports eight additional cases. 
Welch states that the dose of serum to be used 
depends upon the urgency of the case, but that 



122 THE HYPODEEMIC SYKINGE. 

one is likely to err on the side of too small 
doses. It is advisable to begin with at least 
10 c.c. and repeat three times a day if the 
infant is bleeding only moderately. In severe 
cases it should be given every two hours, and 
in larger quantities if necessary. It is very 
important to begin the treatment at the first 
indication of bleeding. However insignificant 
it may appear, slight bleeding of the umbilical 
cord, if not stopped immediately, may be ac- 
companied by fatal internal hemorrhage. 

The author states that normal blood serum 
administered hypodermically gives excellent re- 
sults in the treatment of tuberculosis, and cites 
Wright. According to Wright, normal blood 
serum contains more opsonin than that of a 
tuberculous person, and Welch believes that 
normal serum exerts its favorable action by 
increasing phagocytosis. 

DOSAGE. 

Dejardin (Internat. Med. Ann. 1909; Br. 
Med. Jour. Dec. 12, 1908) states that in adults 
from 10 to 20 c.c. of fresh serum will suffice for 
a venous, and from 20 to 30 c.c. for a subcut- 
aneous injection. If it be necessary, a second 
injection may be practiced after an interval 
of two days without any bad results. In 
children half these doses should be used. 

Leary (Boston Med. & Surg. Jour. 1908, pp. 
33, 73; Am. Jour. Med. Sci. Nov., 1908) reports 
a series of 20 cases in which rabbit serum was 
used in hemorrhage occurring in jaundice in 



THE HYPODEKMIC SYRINGE. 123 

the newly born and with uterin, typhoid, and 
purpura cases. In 15 of the patients hemorr- 
hages had already occurred. In the remaining 
five the remedy was used as a prophylactic 
measure. The subcutaneous route is preferred 
for all injections, 30 c.c. being the dose given. 
He considers his series of cases too small to 
permit of drawing conclusions, but he pleads 
for a wider use of the agent under the condi- 
tions enumerated in his paper. 

USE OP OTHER SERUM THAN THAT OF 
THE HORSE. 

Leary states that the best sources are human 
blood and the blood of the horse and rabbit. 
He believes that bovine serum should not be 
used because, when injected, it is likely to 
cause symptoms, such as high fevers, rigors, 
cyanosis, vomiting, and pain in the head and 
spine. The other serums have not, the author 
asserts, caused any trouble either immediate 
or remote. 

In three cases of hemophilia, using the 
dosage suggested by Weil, viz., 15 c.c. of fresh 
serum for an adult, injecting directly into a 
vein, or 30 c.c. if given subcutaneously, results 
were as follows : 

In the first case, 30 hours after the injection 
of 20 c.c. of fresh rabbit serum the blood clotted 
in a minute, while before, through clotting 
time was 21 minutes. Fifteen days later the 
clotting time was again 30 minutes. The other 
two cases were severe forms of hemophilia In 



124 THE HYPODEBMIC SYEINGE. 

two brothers, but while the clotting time was 
reduced "in vitro' ' the intravenous injections 
of 10 c.c. of human serum had no influence. 

Trembur (Mitteil. A. D. Grenzeb. D. Med. u. 
Chir. 1909, xx, No. 5) found that subcutaneous 
injections of fresh serum of sheep and rabbits 
were of great benefit in a case of severe hemo- 
philia in a young girl where local treatment 
with tampons and gelatin failed to control the 
bleeding. 

COMPARATIVE VALUE OF NORMAL 

SERUM AND OTHER AGENTS IN 

THE TREATMENT OP 

HEMOPHILIA. 

Wirth (Weill, klin. Woch. 1909, No. 3) has 
found 45 articles on the subject of the internal 
methods of hemostasis. He reviews them all, 
with special regard to the use of serum in 
hemophilia. His analysis shows that the re- 
sults of gelatin, calcium, strontium, ovarian, 
and other organ therapy, have been disap- 
pointing, although an occasional success has 
been realized. Far better results have been 
obtained with subcutaneous or intravenous in- 
jection of fresh normal serum, as suggested by 
Weil. 

Bienwald in 1897 reported the arrest of 
hemophilic hemorrhage by local application of 
normal human serum. He drew some blood 
from the child's grandmother and as a last 
resort filled the wound in the left temple with 
the blood. The foreign blood coagulated in 



THE HYPODERMIC SYRINGE. 125 

the wound, and the hemorrhage was arrested. 
Twenty cases have been published in which in 
jection of serum more or less completely ar- 
rested hemophilic hemorrhage. Only two cases 
have been reported in which no benefit was 
derived (Benzani and Mauclair). The effect 
of the serum does not last over a month. The 
local action of the serum is also considerable, 
sometimes rendering repetition of the injection 
unnecessary. 



CHAPTER IX. 

Bacterins. 

It will not be necessary to go into detail 
relative to the theory of use of bacterins, or 
bacterial vaccines, other than to call attention 
to the fact, as demonstrated by Sir. A. E. 
Wright, and others, that a certain number of 
killed, pathogenic bacteria, thrown into the 
system, will bring about the production of anti- 
bodies, destructive to the organisms present. 
These bacterins, or vaccines, as has been shown 
by Wright, convert the bacteria present, 
through the action of opsonins, into such a 
form as to render them easy of absorption and 
digestion by the phagocytes. To further the 
effect of the bacterins, Wright urges the use 
of sodium citrate, both internally and locally 
to the site of infection, in that this drug favors 
the breaking down of the wall thrown about 
the focus and thus allowing the bacterin- 
carrying-blood easier access to the point of in- 
vasion. The Bier method of induced, or arti- 
ficial, hyperemia is likewise of use in connec- 
tion with the introduction of the bacterins, as 
are massage, incision of the infected area and 
the applications of hot saline solution. 



128 THE HYPODERMIC SYRINGE. 

Primarily the autogenous bacterins, manu- 
factured from the discharges obtained directly 
from the infected area of the patient, were em- 
ployed, and this method, where convenient and 
possible, is followed to some extent at the 
present time, but, as a rule, the ready pre- 
pared, or stock, bacterins are employed, as it 
has been found that they are relatively active, 
and frequently are more satisfactory than are 
those of the autogenous sort. But few phy- 
sicians are equipped to manufacture the auto- 
genous bacterins, and the cost of manufacture, 
and the fact that those made in this manner 
may be contaminated with other than the 
strain of bacteria desired, and that the stock 
bacterins are invariably of pure and undefiled 
strain, make the latter preferable. Time like- 
wise figures. Stock bacterins are always at 
hand and ready for use at a moment's notice, 
while it takes several hours to prepare those 
of the autogenous type, and in some cases this 
loss of time may work havoc with the patient. 
In many instances the stock vaccines are em- 
ployed in the beginning to be followed with 
the autogenous later on, and in such instances 
the reports justify the procedure. 

In order that the bacterins, or vaccines, may 
be employed properly, it goes without saying 
that he who administers them must know with 
what sort of infection, and that absolutely, he 
has to deal. A strepto-bacterin given in the 
face of a staphylococcic infection would be 
worthless; the use of the Neisser-bacterin, in 



THE HYPODEEMIC SYRINGE. 129 

cases of gonorrhea with mixed infection, while 
giving some slight reaction, would not be as 
satisfactory as the Neisser-bacterin mixed. 
Consequently, in the treatment of the infections 
by the bacterin method it is of imperative im- 
portance that the microscope be employed in 
the perfection of diagnosis. Because of this 
fact, bacterin therapy has undoubtedly added 
much to scientific therapy, in fact, has done 
much to rescue medicine from the ranks of 
empiricism. When employed absolutely as in- 
dicated, the bacterins become specifics, in that 
they combat certain known etiologic factors 
of disease. 

Not only have the bacterins a curative effect, 
in the face of infective invasion, but it has been 
found that many of them, injected into the 
healthy individual, serve as immunizing agents, 
as is witnessed by the success gained through 
the use of typhoid-bacterin in immunizing 
against typhoid fever. Such immunity is car- 
ried over a considerable period, and in the 
armies of the world, which have been so im- 
munized, epidemics of this disease do not occur, 
as was the case prior to immunization. No 
matter under what conditions the soldiers are 
placed, the cases of typhoid developing have 
become a rarity, which was not true prior to 
the discovery of this method. It is very proba- 
ble that other infections will be overcome in 
like manner, as the bacterins become better 
understood. As there is little, or no danger 
in the introduction of the bacterins into the 



130 THE HYPODEKMIC SYEINGE. 

system, they may be employed without fear of 
untoward results. 

In their application the bacterins are in- 
jected into those sites, if possible, where the 
lymph will drain through or past the local 
lesion, although this is not absolutely neces- 
sary, or important. If they enter into the cir- 
culation, they will eventually be carried to the 
site of invasion and be as equally active, as 
though thrown directly into the infected focus, 
that is, providing the conditions are such as 
enable their entrance into such focus. If the 
suggested use of sodium citrate is carried out, 
the barriers will be sufficiently broken down 
as to allow of the entrance of the antibodies, 
or opsonins, within the site of infection. The 
theory of dosage is the administration of 
enough to produce sufficient antibodies to over- 
come the toxic effects of the pathologic germs 
present; to increase the opsonins and other 
antibodies. That bacterins may be active, when 
administered orally, has been suggested, but 
not sufficient investigation has been done in 
this direction as to either substantiate such 
fact, or to give any idea as to proper dosage. 
As the hypodermic method has been found 
sure, in the vast majority of instances, it will 
undoubtedly continue to be the popular method 
of exhibition of the bacterins. There is but 
little, if any, discomfort attending their hypo- 
dermic administration, and as they are not 
destroyed, either in part or whole, when thrown 
into the subcutaneous tissues, as may be the 



THE HYPODERMIC SYEINGE. 131 

case when given by mouth, their ultimate ac- 
tivity is better assured. 

It will not be necessary to discuss the method 
of manufacture of the bacterins at this time, 
as full descriptions of the method of prepara- 
tion have been published time and again. The 
discussion of action of these agents will be 
taken up as each individual bacterin is taken 
up and considered. 

Acne-Bacterin. Staphylo-Acne-Bacterin — 

There are three classes, from a bacteriologic 
standpoint, of acne. In the first are those cases 
wherein the comedo is the predominant symp- 
tom, in which, in some instances the process has 
passed on to the pustular and indurated stage. 
In this class the acne bacillus is the primarv 
infective agent, while the staphylococcus plays 
a secondary part. The acne-bacterin is indicat- 
ed in this class. 

In the second class, where the induration and 
pustules are marked; it is found that both the 
acne bacillus and staphylococcus are practical- 
ly equally active in causing the inflammatory 
process. Here the mixed vaccines of the acne 
bacillus and staphylococcuc, or staphylo-acne- 
bacterin, is indicated. The staphylo-bacterin 
is indicated in those more acute forms, where 
there is a greater tendency toward furuncul- 
osis, as the microscope shows that the staphy- 
lococcus is the chief etiologic factor. In this 
class, however, the acne bacillus should not 
be overlooked or forgotten and when found 



132 THE HYPODERMIC SYRINGE. 

the acne-bacterin should be added to the treat- 
ment. 

As a synergist, both the local and internal 
use of sodium citrate should be remembered, 
in that this agent favors softening of the wall 
thrown by nature about the infected area, and 
allows of the easier access of the blood to the 
focus of infection, with consequent greater ac- 
tion of the phagocytes and opsonins or other 
antibodies. 

The dose of the acne-bacterin, initially, is 
from 5,000,000 to 10,000,000 of the killed bac- 
teria. That of the staphylo-acne-bacterin is 
from 150,000,000 to 300,000,000 of the killed 
staphylococci and from 25,000,000 to 50,000,000 
of the killed acne bacilli. The interval between 
inoculations is from one to two weeks, and the 
relative dose is indicated by the existing con- 
ditions. The dose should be worked up to 
that point, the "Negative phase," or rather 
just failing to meet that point, which is signi- 
fied by increase of the eruption and feeling of 
malaise. 

The use of the staphlo-bacterin will be con- 
sidered at greater length, in connection with 
the treatment of this disease, under the dis- 
cussion of this vaccine. 

Coli-Bacterin — In Working Bulletin No. 1, 
Third Edition, June, 1911, the coli-bacterin is 
discussed very fully, and what is said there is 
repeated as follows: 

Mixed Infection — The bacillus coli communis 
group of affections is especially associated 



THE HYPODERMIC SYEINGE. 133 

with diseases of the abdominal and pelvic or- 
gans, either alone or in conjunction with some 
other bacterium, such as streptococcus, sta- 
phylococcus, pneumococcus, micrococcus tet- 
rangeous or bacillus pyocyaneus Among the 
conditions which are set up which are more or 
less amenable to vaccine therapy, are peritoni- 
tis, cystitis, urethritis, pyelitis and pyelone- 
phritis, endometritis, enteritis, perityphlitis, 
cholecystitis, subphrenic and hepatic abscess, 
fistula in ano and even empyema and suppura- 
tive periostitis. 

Coli-bacterin has been successfully used by 
Wright (Path. So. Jan. 16, 1906) in the treat- 
ment of cholecystitis, acute colon infection of 
the biliary passages and other colon infections. 

Western (Path. So. Jan. 16, 1906) success- 
fully treated cystitis which had not markedly 
improved under any other treatment. 

Allen (Vaccine Therapy and Opsonic Treat- 
ment) obtained excellent results in cystitis 
complicating tuberculosis of the bladder and 
kidneys and says that the prognosis is almost 
uniformly favorable in sinus cases, whether 
coming from the region of the liver, gall-blad- 
der, appendix, pleura or bone, provided that 
the appropriate surgical measures can also be 
pursued. 

Acute Nephritis and Pyelitis of Pregnancy — 
The same author states that in acute nephritis, 
and especially in the pyelitis of pregnancy, re- 
course should be taken to vaccine treatment 
when colon bacilluria is present. He also 



134 THE HYPODEEMIC SYBINGE. 

recommends it in appropriate cases of puer- 
peral septicemia. 

Pre-Operative Inoculation — Wright and his 
co-workers advise the use of coli-bacterin prior 
to an abdominal operation, where contamina- 
tion from the infected focus is feared. He 
also uses it in gonorrheal infection especially 
associated with the streptococcus and straphy- 
lococcus. 

Hale White (Pro. of the Roy. So. of Med. 
1910, vol. iii) obtained recovery in a case of 
profound septicemia. 

Coli-Bacterin in Gonorrhea — Butler Harris 
(Pro. of the Roy. So. of Med. 1910, vol. iii) 
states that simple gonorrheal and colon infec- 
tion appear to yield very readily after a few 
inoculations. He reports cures of colitis which 
had been passing mucus and occasionally blood. 

Emery (Ibid) finds that as a rule effects fol- 
lowing the use of coli-bacterin in colon infec- 
tion are marked and immediate. 

Inman (lb.) states that in some cases all of 
the bacilli disappear from the urine, although 
the bacilli may persist long after the symptoms 
have disappeared. 

J. C. Briscoe (Lancet, Oct. 30, 1909) recom- 
mends bacterin treatment in obstinate cases. 

Diabetes — Wright (Practitioner, May, 1908) 
suggests that diabetes may be caused by a bac- 
terial infection and states that bacterial the- 
rapy is indicated in the treatment of these 
cases. 



THE HYPODERMIC SYRINGE. 135 

It has been recommended that the bowels 
should be thoroughly evacuated, that the 
urine be made alkaline and that five or ten- 
grain doses of hexamethylene be employed. 

Dosage— Allen (Path. So. Jan. 16, 1906) 
states that the initial dose should not exceed 
50 million and recommends ten-day intervals 
between doses. In sinuses due to colon infec- 
tion, a dose of 25 million should not be ex- 
ceeded. 

White and Eyre (Pro. of the Roy. So. of Med. 
June, 1909, p. 146) used an initial dose of 5 
million (autogenous vaccine), four days later 
a dose of 30 million and ten days later one of 
250 million. 

Butler Harris (Practitioner, May, 1908, p. 
647) finds that a dose of 5 million given a 
week after the period and repeated a week 
before the next will often cure slight endome- 
tritis with cervical catarrh w T hen the colon 
bacillus is present. Treatment should be con- 
tinued at least six month. 

Friedlaender-Bacterin — Quoting from Work- 
ing Bulletin No. 1, we find the Friedlaender- 
bacterin discussed as follows: 

Respiratory Catarrh and Sequelar — Within 
the past three or four years much study has 
been given to the bacteriology of catarrhal af- 
fections of the respiratory organs. The con- 
nection between these catarrhal affections and 
infections of greater gravity, such as pneu- 
monia, asthma, bronchitis, disease of the mid- 
dle ear, arthritis, septicemia and the second- 



136 THE HYPODERMIC SYRINGE. 

ary infections of tuberculosis, has been definite- 
ly established. 

Causative Organisms — The bacteriology of 
colds and respiratory catarrhs has been deter- 
mined with more or less exactitude. The 
pioneer workers in this field are Cantley, Dunn 
and Gordon, Bezancon and De Jong, Prosser 
"White, Cardone, Benham and Allen. The re- 
sults of their investigations show that the 
causative organisms in these infections are the 
bacillus influenzae ; the bacillus of Friedlaender 
and its allies, including, possibly, the B. pro- 
teus, the B. Septus (or coryzae segmentosus), 
the micrococcus catarrhalis, M. paratetragenus, 
pneumococcus, and possibly the streptococcus 
salivarius and the staphylococcus. 

Friedlaender Bacillus — The bacillus of 
Friedlaender and its allies are manifest in 
acute nasal catarrh, ulcerative pharyngitis, and 
tonsillitis, in chronic nasal catarrh, also in 
otitis media and sometimes in pneumonia and 
in abscesses. It has been noticed that the elim- 
ination of the Friedlaender bacillus by bacterial 
therapy may be succeeded by an outburst of 
infection due to other germs such, for example, 
as the micrococcuss catarrhalis, which has been 
previously held in restraint. Two or three 
doses of the appropriate bacterin will in all 
probability complete the cure. 

Chronic Gleet — The bacillus of Friedlaender 
is also found in chronic gleet. Such cases are 
usually mixed infections and should be treated 
as such. Pneume-bacterin and Neisser-bacterin 



THE HYPODEEMIC SYRINGE. 13? 

and even cultures of living lactic acid bacteria 
have been successfully employed in the treat- 
ment of some of these cases. 

Dosage — Allen states that the dosage of 
Friedlaender vaccine depends entirely upon 
the patient's power of response. According 
to that author "no upper limit of dosage can 
possibly be assigned. Thus, until recently, I 
was afraid to exceed a dose of 500 million of 
vaccine of the bacillus of Friedlaender. En- 
couraged by the effects of large doses of sta- 
phylococcic vaccine in obstinate cases of 
acne, I decided to try one billion. In each of 
three cases, the result was almost immediate 
cure.'' 

The interval between doses should be three, 
five or seven days, remembering that the more 
acute the infection, the smaller and more fre- 
quently repeated the dose, and that in chronic 
conditions the dose should be larger and re- 
peated at longer intervals. 

Neisser-Bacterin. Neisser-Bacterin Mixed— 
Neisser-bacterin is a vaccine made from killed 
gonococci. It is indicated in those conditions 
due to the gonococcus invasion, as urethritis, 
peri-urethritis, prostatitis, vesiculitis, cystitis, 
epidydimitis, orchitis, vaginitis, endometritis, 
salpingitis, peritonitis, conjunctivitis, endo- 
carditis, arthritis, and in some cases, pleurisy 
and septicemia. 

The recognition that gonorrhea is other than 
a local disease, and that constitutional treat- 
ment is practically invariably required has 



138 THE HYPODERMIC SYRINGE. 

paved the way for the use of the bacterins in 
this disease. Many of the constitutional con- 
ditions associated, which in former years failed 
to show improvement under medical treatment, 
now submit to application of the vaccines. 

The Neisser-bacterin mixed, is a polyvalent 
vaccine, made from the mixed bacteria found 
either in the prostatic fluid or pus in chronic 
conditions, and is employed in combating con- 
ditions of the latter class, the mixed infections 
which occur after the primary action of the 
gonococcus has disappeared, and where, in 
many instances that germ is not demonstrable 
either by the microscope or by culture. In 
cases of this sort, in addition to the gonococcus, 
if present, there are to be found the pyogenic 
staphylococci in the majority of instances, with 
the streptococci in fifty per cent, while in a 
lesser number is found the pseudo-diphtheria 
bacillus. 

Irons, in the Journal of Infectious Diseases, 
June 4, 1908, calls attention to the value of 
the Neisser-bacterin by the following remarks: 

"A typical gonococcus reaction is character- 
ized by a rise in temperature, often only slight ; 
an increase in pain and tenderness in the af- 
fected joints, with occasionally some increase 
in swelling, and a variable degree of malaise. 
The symptoms follow the injection in from 
eight to twelve hours, and commonly last 
about twenty-four hours. Frequently there is 
a decided tenderness at the site of the injec- 
tion, greater than occurs after the inoculation 



THE HYPODERMIC SYRINGE. 139 

of the same dose of the same preparation in 
normal subjects. Occasionally there is a 
marked redness and edema lasting from 
twenty-four to forty-eight hours. In a case of 
periurethral abscess of gonococcal origin with- 
out secondary infection, which was under sur- 
gical treatment with drainage, an injection of 
500,000,000 cocci was followed in eighteen 
hours by moderate swelling and tenderness at 
the site of needle puncture, and also marked 
increase in redness and tenderness about the 
wound. There was no coincident retention of 
pus or local secondary pus infection to account 
for the phenomenon, and the wound returned 
to its normal condition in twenty-four hours. 
There is usually a slight increase in leucocy- 
tosis in the first twenty-four hours after in- 
jection. 

"The frequency with which these clinical 
phenomena occurred suggested the possibility 
of utilizing the reaction in the diagnosis of 
obscure cases of arthritis in which the gono- 
coccus was the suspected cause. The effects 
of the injection of dead gonococci into patients 
not suffering from gonococcus infection were 
accordingly studied. Eight adults in whom 
there was no history or sign of gonococcus in- 
fection were given injections of 500,000,000 
dead gonococci. In none of these cases was 
there any local change other than that follow- 
ing ordinary hypodermic puncture, and no 
fever or constitutional disturbance was ob- 
served. In a case of pyorrhea alveolaris with 



140 THE HYPODERMIC SYRINGE. 

subsequent general infection and painful 
swellings over the extremities, there was no 
increase of fever or local symptoms following 
the injection. A case of gout with active joint 
involvement showed no local or general changes 
after a dose of 500,000,000. Leucocytes before 
injection, 13,200; eighteen hours after injec- 
tion, 13,000. Temperature was normal through- 
out. A case of articular rheumatism showed 
no reaction after a dose of 500,000,000. There 
was no increase in leucocytosis and the tem- 
perature chart showed no abnormal variations. 
A case of acute arthritis with pericarditis was 
thought possibly gonococcal in origin. There 
was no reaction after a dose of 500,000,000. 
Cultures from the blood and from a small 
amount of fluid aspirated from the knee re- 
mained sterile, and the prostatic fluid con- 
tained no gonococci. The subsequent course 
was typical of rheumatic fever. In four other 
cases of acute and subacute articular rheuma- 
tism there was no reaction after injection of 
500,000,000 cocci. 

"In a number of suspected gonococcus cases 
the reaction was of value in making an early 
diagnosis. A case of monoarticular arthritis 
with effusion in the knee, in which gonorrheal 
infection was denied, was given an injection of 
500,000,000. The evening temperature, which 
previously had reached only 100°, rose to 
101.8°, and the joint pains increased. The knee 
was aspirated, and the gonococcus isolated in 
pure culture from the fluid. A case of chronic 



THE HYPODERMIC SYRINGE. 141 

arthritis which had resisted all treatment was 
given an injection. A slight rise in tempera- 
ture, with some increase in joint pain followed. 
The prostatic fluid was found to contain gon- 
ococci, and the subsequent course was that of 
gonorrheal arthritis. A patient who had 
suffered from extensive gonococcus arthritis 
had been bed-ridden for one year. There was 
practically no motion in the knees. After an 
injection of 500,000,000, the temperature, which 
for weeks had been normal, rose to 99.5°, and 
the patient complained of malaise and increased 
pain in the joints. A patient with aortic an- 
eurism who denied gonorrheal infection, had 
been selected for control experimental inocula- 
tions. After an injection of 500,000,000 cocci, 
the temperature, which had been uniformly 
normal, rose to 100°P. without any other ap- 
parent cause, returning to normal the next day, 
without any subsequent rise. The prostate was 
examined and found to be large and somewhat 
tender, and the secretions contained numbers 
of leucocytes with typical intracellular gon- 
ococci. 

"The reliability of the clinical gonococcus 
reaction as a diagnostic procedure will be de- 
termined only after many tests. It has many 
points in common with the tuberculin reaction, 
and similarly too there may well be cases of 
gonococcus infection found which do not re- 
spond. It appears, however, to be well worth 
a trial. Should the reaction prove to be reli- 
able, a valuable and much needed aid will be at 



142 THE HYPODEEMIC SYRINGE. 

hand for the diagnosis of obscure joint, syn- 
ovial and periosteal diseases." 

Aronstam (J. A. M. A. Oct. 24, 1908) says 
that while the Neisser-bacterin may cause a 
recrudescence in dormant gonococcic arthritis, 
probably acts materially to shorten its dura- 
tion. 

The necessity of using the mixed bacterins 
in chronic conditions is observed by von Not- 
thafft (Die chron. Gon. der mann. Harn. und 
ihre Kompl. II verm, und verb. Auflage, Leip- 
sig, 1910. First Edition, Part 3, p. 137) as fol- 
lows: 

"1. Already in the second half year after 
infection the gonococcus in demonstrable in 
the prostatic secretion in no more than 73 per 
cent, of the cases. This figure follows in the 
third half year of 50 per cent., in the fourth to 
18 per cent., in the fifth to 6 per cent. From 
the end of the third year on, the gonococcus 
can no longer be found in the prostatic secre- 
tion. 

"2. Already in the second half year other 
bacteria than the gonococcus appear in the 
prostatic secretion. In the fourth half year 
pure gonococcus infections are no longer 
demonstrable." 

Dosage — In the discussion of this part of 
the question, it seems to be the consensus of 
opinion that it should be based upon the ability 
of the patient to bear the effect of the Neisser- 
bacterin. It should be realized that toxic con- 
ditions are liable to follow large doses, especial- 



THE HYPODERMIC SYRINGE. 143 

ly of freshly prepared bacterin, and that the 
former large doses of 100,000,000 to 500,000,000 
are liable to produce undesirable effects. The 
dose suggested today ranges from 1,000,000 to 
5,000,000 initially, this to be increased or de- 
creased, according to effects produced. In 
some instances the smaller dosage is never in- 
creased from the beginning, while in others, in 
order to obtain satisfactory results a marked 
increase is necessary. If a large dose has been 
injected and bad results follow, in so far as 
symptoms are concerned, no real harm should 
follow, but the next injection should be smaller 
and the latter not increased as long as there 
is improvement in the condition. The unde- 
sirable effects are aggravation of the symp- 
toms, rise in temperature, malaise, etc., which 
show a toxic dose has been given. 

In the administration of the Neisser-bacterin 
mixed, the method is to inject primarily a mix- 
ture containing 100,000,000 each of staphylo- 
aurcus, staphylo-albus and staphylo-citreus, 
and 50,000,000 each of streptococci, bacillus 
coli, pseudo-diphtheriae and gonococcus, which 
may be increased or diminished, the condition 
of the patient giving the indication. No in- 
crease is necessary or desirable, if there is im- 
provement. If there are symptoms of a decided 
negative phase, the following dose should be 
reduced. The interval between injections is 
from 5 to 7 days, and here again does the 
condition indicate as to whether the interval 
should be shortened or lengthened. 



144 THE HYPODERMIC SYRINGE. 

Neoformans-Bacterin — It is believed by 
some, and disputed by others, that the Micro- 
coccus Neoformans, is the cause of cancer. Re- 
cently a vaccine, known as neoformans-bacterin, 
has been offered. Relative to the organism, 
and the bacterin prepared therefrom, we find 
the following remarks in Working Bulletin No. 
1, Third Edition, June, 1911 : 

Micrococcus Neoformans and New Growths 
— Doyen, a French surgeon, isolated from new 
growths a micrococcus which he believed to 
be the specific cause of cancer, and which he 
named neoformans. This work Doyen did not 
make public for ten years, as he believed med- 
ical science was not ready to accept anything 
so advanced. 

While the work of other investigators seems 
to disprove the theory that this micrococcus 
may itself be the cause of cancer, it is believed 
by many that the micrococcus neoformans is 
frequent cause of intercurrent infections. 

Ulcerative Cancer — This micrococcus is 
found in a large proportion of malignant new 
growths, especially those which have ulcerated. 
The effect of these ulcerations is to frequently 
aid the cancerous growth by so weakening the 
tissues that the malignant growth is able to 
spread more rapidly. 

Arguing from this point, Wright and others 
have made use of a neoformans vaccine for the 
treatment of ulcerated cancerous conditions, 
with sometimes remarkably beneficial results. 

Restricted Uses — When one has seen a num- 



THE HYPODERMIC SYRINGE. 145 

ber of cases in which there has been marked 
benefit following the use of a certain remedy, 
it is difficult not to become enthusiastic and 
believe that equally good results would be ob- 
tained in all other cases with the remedy. In 
probably no disease has this condition been 
more true than in the treatment of cancer. 
Neoformans vaccine will benefit patients suffer- 
ing from some forms of malignant new growths, 
but it is too much to claim that the vaccine will 
cure cancer or that even benefit can be obtained 
in every case. If this claim is made, some 
notable failure will cause the vaccine to fall 
into unearned disrepute. 

Neoformans Serum, Mixed Infection — A 
Paine and D. J. Morgan (Lancet, April 7, 1906) 
review Doyen's theories as to the occurence of 
his so-called " micrococcus neoformans' ' in 
malignant growths, and the various steps lead- 
ing up to the elaboration of his serum. Of 
nine cases treated by them with serum injec- 
tions, no effect on the course of the disease 
was noted in four. In two, the injections were 
followed by severe pain, and in three by 
severe constitutional disturbances. Concern- 
ing the micrococcus neoformans, the authors 
note that it is often present with other micro- 
cocci in malignant turners but in their opinion 
not in sufficient numbers or with a constancy 
to enable it to be regarded as the etiological 
facter in the evolution of these growths. In 
their hands, the inoculation of animals with 
this organism has been followed, not by the 



146 THE HYPODERMIC SYKINGE. 

formation of neoplasma, but by the expression 
of inflammatory reactions. 

Cancerous Cachexia — C. Jacobs and V. Geets 
believe that there exists in cancerous cachexia, 
a specific micro-organism, the micrococcus neo- 
formans of Doyen, and report cures from its 
use. They summarize their results in 46 cases 
as follows: "Cure," maintained after several 
months, 7; lasting improvement, 12; transient 
results, 7 ; no results, 12 ; still under treatment, 
9. 

Dr. Alexander J. Anderson, of Newport, R. 
I., published in the American Journal of 
Dermatology, a report of a case of carcinoma 
of the kidney which improved under the use 
of neoformans vaccine. The case was still 
under treatment. 

Accessory Treatment — It should not be for- 
gotten that Doyen uses fulguration and other 
methods of treatment in conjunction with his 
vaccine therapy; and furthermore, that the ex- 
act nature of the neoformans vaccine employed 
by him has never been published. 

Dosage — The intitial dose of neoformans- 
bacterin is given as 25 to 50 millions. 



CHAPTER X. 

Bacterins. 

(Continued) 

Antipneumococcic Serum (Anti-Pneumonic 
Serum) . Pneumo-Bacterin. Pneumo-Bacterin 
Mixed — As both antipneumonic serum and the 
pneumo-bacterin and pneumo-bacterin mixed 
as employed in the treatment of pneumonia, 
and pneumonic infection, and as each has its 
place, they will be considered under one head. 

As the information contained within Work- 
ing Bulletin No. 7 has been gathered from all 
sources, impartially, this will be quoted to a 
considerable extent in the discussion of these 
agents. 

Pneumo-Bacterin — This is a suspension in 
sterile physiological salt solution of the bac- 
teria secured from 24-hour agar cultures of the 
pneumococcus (Frankel). The microorganisms 
are rendered sterile by subjection to a tempera- 
ture of 60° C. for one hour. The suspension 
is standardized by bacterial count and diluted 
so that it contains approximately a fixed num- 
ber of pneumococci per cubic centimeter. A 
small percentage of trikresol (0.25 per cent.) 
is added as a preservative. 



148 THE HYPODEEMIC SYBINGE. 

Polyvalency — The cultures used in preparing 
bacterins contain bacteria originally obtained 
from a large number of infectious patients. 
Many species of bacteria comprise numerous 
subvarieties or strains. There may be but little 
apparent difference microscopically, yet biologi- 
cal experiments show different reactions which 
indicate that the rule of specifity obtains, at 
least to a certain extent, even in these miner 
subdivisions. It is principally for this reason 
that autogenous bacterins (those made from 
specimens secured from the patient to be 
treated) were at first thought to be essential. 
Later experience has demonstrated that the 
preparation of autogenous bacterins consumes 
so much time and expense as to make them in 
many cases both useless and unavailable. 
Stock bacterins, on the other hand, composed 
of cultures of bacteria secured from numerous 
patients and comprising as many strains as 
possible (or polyvalent) have produced most 
satisfactory results. The use of autogenous 
bacterins may be said in general to have found 
its proper place as a form of treatment in ob- 
stinate or chronic cases where the stock bac- 
terins have been tried without satisfactory re- 
sults. Even in these cases the lack of efficiency 
of the bacterin may perhaps in many instances 
be attributed to the inability of the antibodies 
to reach the part affected, improper dosage, 
inaccuracy of diagnosis. In many cases the 
employment of artificial hyperemia, etc., may 
bring about the results desired, 



THE HYPODERMIC SYKXNGE. 



149 



Theoretical Considerations Relative to Bac- 
terin Therapy — Bacterin (vaccine) therapy in 
general is based upon Wright's opsonic theory 
of immunity. According to MetehnikofTs 
teachings bacteria which gain entrance into 
the blood or tissues are destroyed chiefly by 
the phagocytes. Wright demonstrated that be- 
fore this can occur the bacteria are acted upon 
by certain bodies in the blood, which he called 
"opsonins." These are specific (i.e., a pneumo- 
coccus opsonin will attack only that micro- 
organism and not other bacteria), and are 
formed under the stimulus of the presence of 
bacteria or their products of metabolism. By 
means of the "opsonic index' ' it may be shown 
that with the increase or diminution of the 
specific opsonin content of the blood the phago- 
cytic power of the leucocytes is correspondingly 
increased or diminished. 

Artificial Stimulation of Opsonic Production 
— Holding the view that opsonic bodies are 
formed by a protective reaction of the fixed 
cells to the attacks of parasitic microorganisms, 
Wright developed a method of artificially in- 
creasing the specific opsonic content of the 
blood by injecting into healthy tissues bacteria 
which have been rendered incapable of 
multiplication, i.e., "killed bacteria." The 
formation of opsonins is thus stimulated and 
the "killed bacteria" are consequently ingested 
by the phagocytes. The body cells, however, 
produce opsonins greatly in excess of the quan- 
tity necessary for the destruction of the sterile 



150 THE HYPOBEBMIC SYBINGE. 

microorganisms present at the site of injection, 
and the surplus enters the blood and other body 
fluids and increases their specific opsonic con- 
tent. 

Opsonic Production in Spontaneous Recovery 
— The initial attack of most infections is of a 
local nature. This is followed by multiplica- 
tion of the bacteria and destruction of tissue, 
and in some cases the flooding of the body fluids 
with bacteria and bacterial toxins on one hand 
and increasing migration of phagocytes and the 
formation of opsonins and other antibodies on 
the other. The growth of the bacteria under 
favorable circumstances may be for a time 
much more rapid than the formation of anti- 
bodies, and a severe illness ensues. Great de- 
struction of tissue may take place as well as 
general intoxication from the absorption of de- 
composition products and toxins. But when 
spontaneous recovery occurs, the production 
of antibodies proceeds steadily, and, it would 
seem, with increasing rapidity, until finally a 
time is reached when there are sufficient opson- 
ins and other antibodies to enable the phago- 
cytes to overcome the bacteria completely and 
to neutralize their toxins. Thus it becomes 
evident that if during the early stages of a 
disease the formation of antibodies in some 
healthy portion of the body is artificially in- 
duced, and these are carried to the infected 
area, rapid destruction of the bacteria will take 
place and the disease process aborted. 

This, in fact, constitutes the basis upon which 



THE HYPODERMIC SYRINGE. 



151 



the theory of baeterin, or vaccine, therapy 
rests. In the words of Wright, it consists in 
exploiting "in the interest of the infected tis- 
sues the unexercised immunizing capacity of 
the uninfected tissues." 

Active Immunization in Treatment — Employ- 
ing Wright's "opsonic index,' ' which is simply 
a comparison of the relative phagocytic power 
of the specimen of blood being investigated 
(under test) with that of normal blood, it may 
be shown that in a person already suffering 
from an infection, an injection of killed bac- 
teria of the same species as that producing the 
disease causes immediate temporary reduction 
of the specific opsonic content of the blood. 
This is called the opsonic negative phase. It 
is followed, however, in a very short time by 
an increased opsonic production, which con- 
tinues until it has reached a point considerably 
above that originally present. This is known 
as the opsonic positive phase. While the oc- 
currence of the opsonic negative phase is not 
necessarily accompanied by a corresponding 
clinical aggravation of symptoms, when the 
opsonic positive phase sets in a distinct im- 
provement in the condition of the patient is 
usually observed. After the opsonic positive 
phase has reached its height the opsonic con- 
tent of the blood gradually diminishes. At 
this time another injection of baeterin is indi- 
cated. The procedure is then continued until 
a cure of the primary infection is obtained. 

Dosage and Method of Administration — In 



152 THE HYPODERMIC SYRINGE. 

treatment according to Wright, the produc- 
tion of a clinical negative phase should be 
avoided. The success of the treatment depends, 
indeed, to a great extent on the careful regula- 
tion of dosage and the ascertaining of the max- 
imum dose tolerated without ensuing clinical 
negative phase, i.e., aggravation of symptoms, 
rise of temperature, chills, and a general feel- 
ing of malaise. Aside, however, from the neces- 
sary reduction of dosage, together with the 
possible psychic effect on the patient, no harm 
from the occurence of the clinical negative 
phase has been recorded. In fact, in some ob- 
scure chronic affections it has been deliberately 
produced for diagnostic purposes. 

Fortunately the extensive use of bacterins 
has developed what may be termed an average 
range of dosage. The use of the opsonic index, 
at one time considered the only means of 
properly controlling the dosage, but which is 
a troublesome and time-consuming procedure, 
has been almost entirely dispensed with and in 
most cases reliance is placed upon clinical ob- 
servation for the control of dosage. If the 
patient streadily improves with a repetition 
of the initial dose no increase in dosage should 
be made; when improvement is slow or absent 
the dose should be gradually increased. 

A careful review of the literature shows a 
change in opinion regarding the dosage of 
pneumo-bacterin. The initial dose first recom- 
mended was usually 25 million killed bacteria, 
and that this first dose be gradually increased 



THE HYPODERMIC SYEINGE. 



153 



until the desired results are secured. Leary, 
of Tufts Medical School, commenced with doses 
of 10 million administered every 3 hours, but 
soon changed to 100 million every 24 hours. 
Robertson and Illman employ doses ranging 
from 25 million to 600 million and state that 
the results seem to be more definite with the 
larger doses. Rau found the usual dose of 10 
million to 50 million too small and also advo- 
cates the larger doses. He begins treatment 
with a dose of 50 million, followed in 24 hours, 
if necessary, by 100 million, while in some 
cases 150 million are employed. 

It should always be borne in mind that great- 
er relative benefit may be secured by early 
treatment. Obviously the destruction and al- 
teration of tissue caused by the bacteria or by 
their products, and the exudates often present 
after the disease has progressed for some time, 
may prevent the antibodies from reaching the 
point of infection and thus render them com- 
paratively useless. This, however, may be to 
a great degree overcome in some cases, especial- 
ly in infections of the joints, etc., and chronic 
empyema, or when there are areas of consolida- 
tion remaining after active infection has sub- 
sided, by manipulation and other mechanical 
methods of producing local hyperemia, or by 
the use of medicaments which have the proper- 
ty of lessening the viscosity of the blood e.g., 
citric acid — 40 gr. internally. 

Chronic Cases and Localized Infection, Due 
to the Pneumococcus — Pneumo-bacterin may 



154 THE HYPODERMIC SYRINGE. 

be employed, with success, in other infections 
than pneumonia, such as arthritis, ulcus ser- 
pens, pyorehea alveolaris, and others in which 
it is possible to demonstrate the pneumococcus 
as the means of infection. These will be con- 
sidered at length under the head of "Clinical 
Reports.' ' 

Pneumo-Bacterin Mixed — Is prepared and 
standardized in the same manner as pneumo- 
bacterin, but is composed of several varieties 
of pathogenic microorganisms and is intended 
for the treatment of combined infections due 
to the pneumococcus, streptococcus and sta- 
phylococcus. 

Indications and Use — In practically all cases 
of broncho-pneumonia mixed infection is 
present. Therefore, treatment with a bacterin 
composed of only one organism is not likely to 
be efficacious. For this reason a bacterin which 
contains all the varieties of pathogenic bacteria 
found in a large number of cases is employed, 
and has proved of great value in both treat- 
ment and prophylaxis. It was previously con- 
sidered necessary in mixed infections to have 
the bacterin prepared from the patient (auto- 
genous bacterin). This procedure is necessarily 
slow, and is now the general practice to em- 
ploy a mixed bacterin under the guidance of 
such indications as may be clinically observed 
or which may be elicited by bacteriological 
examination. Mixed bacterins have also been 
very successfully employed in the immuniza- 



THE HYPODERMIC SYRINGE. 155 

tion of persons subject to recurrent attacks of 
respiratory infection. 

Characteristic Clinical Symptoms Produced 
by the Presence of Various Organisms in the 
Respiratory Tract — Allen (Jour. Vaccine. 
Ther. July, 1912) gives the following symp- 
tomatology for the early differential diagnosis 
of infections of the respiratory tract: 

Pneumococcus — This microorganism is capa- 
ble of involving each and every portion of the 
respiratory tract, with rawness of the mucous 
membrane, harsh and dry cough. By the sec- 
ond or third day the infection has begun to 
spread upward into the nasopharynx and down 
into the trachea; on the third and fourth day 
the pharynx and trachea may feel sore, while 
expectoration and nasal discharge becomes 
profuse and mucopurulent. There is consid- 
erable malaise and headache and some rise in 
temperature. Involvement of sinuses follows, 
with a sense of fullness and referred head 
pains, with extension to chest, and moist sounds 
in the bronchi and bronchioles, and muscular 
or pleuritic pains. Finally, the alveoli are 
attacked and definite pneumonia sets in. The 
symptoms may, however, vary on account of 
the fact that the first attack may be located at 
any part of the entire respiratory tract. 

Bacillus Septus — Dryness or tickling of soft 
palate, extending in 24 hours to the nasal 
mucosa, with sneezing and discharge of this 
mucus. The pharynx next becomes involved, 
causing pain in swallowing, and loss of smell 



156 THE HYPODERMIC SYRINGE. 

and taste. Headache, malaise and pyrexia are 
slight. The acute stage subsides in 3 or 4 days, 
while the subacute stage persists, characterized 
by thick but not very purulent mucus, for about 
4 days. 

Micrococcus Catarrhalis — Attacks any point 
of the entire respiratory tract, producing any 
form of inflammation from a nasal catarrh to 
a capillary bronchitis. There is usually an in- 
flamed feeling of the fauces and nasopharynx, 
which is quickly followed by extension into 
the nose and pharynx. There is a thin, pro- 
fuse discharge from the nose, and thin, color- 
less watery mucus from the larynx, impairment 
of voices, cough, and sore feeling in the 
trachea. Deafness exists, the sinuses are usual- 
ly infected, and there is a sense of fullness. 
Toxic absorption produces headache, malaise 
and rise in temperature. The subehronic stage 
commences in 3 or 4 days, and may be present 
for weeks. Profuse mucopurulent mucus may 
be expelled. The lower respiratory passages 
may become involved with the production of 
a troublesome and persistent but not very acute 
infection of the bronchi and bronchioles; 
copious thin, but very tenacious or purulent 
mucus is voided. Infections by this organism 
have a tendency toward chronicity or to occur 
frequently. At times they very closely resem- 
ble infections by B. Influenzae. 

Micrococcus Paratetragenus— The symptoms 
in this infection may resemble closely those of 
Micrococcus catarrhalis, but the favorable 



THE HYPODERMIC SYRINGE. 157 

point of attack seems to be the larynx. There 
is usually huskiness of voice, followed by in 1 
or 2 days by a dry, paroxysmal cough, with 
expulsion of very small bits of clear, tenacious 
mucus. The secretion is not profuse or muco- 
purulent. As a rule, there is no involvement 
of the accessory sinuses. The chief characteris- 
tic is a dry, hacking cough. 

Friendlander Group — The nasal passages and 
adnexia are first attacked, causing sneezing, 
malaise, slight headache and loss of smell. The 
discharge is profuse, usually clear and color- 
less ; and when the antrum or sinuses have be- 
come involved it is mucopurulent. The 
eustachian tube usually escapes infection, and 
subjective noises and deafness do not occur. 
The sore throat and cough are absent. In rare 
cases, in adults, but more commonly in 
children, the bacillus may find its way to the 
bronchi and set up bronchitis or broncho-pneu- 
monia. These infections are likely to become 
chronic. 

B. Influenzae — Is usually associated with the 
pneumococcus. There is extreme malaise, head- 
ache, joint-pains, pyrexia, perhaps rigors. 
Digestive disorders follow, and neuritis, diffuse 
or local; or herpes zoster may appear; in such 
instances the infection is probably systemic 
and may become latter localized in the pulmon- 
ary tissues. 



158 THE HYPODEBMIC SYRINGE. 

CLINICAL REPORTS. 

Pneumonia — Robertson and Illman (Penn. 
Med. Jour. Jan. 1912) give data in regard to 
50 cases of pneumonia, 30 of which received 
only customary treatment and 20 of which 
were given bacterin injections. "Of the 30 
cases not given bacterins, 12 died, or 40 per 
cent. ; of the 20 to whom bacterins were given 
3 died, or 15 per cent.; or excluding a woman 
who died of uremia the mortality in the 19 
cases was 10.5 per cent." The doses employed 
ranged from 25 million to 600 million. Results 
seemed to be more definite with larger doses. 

Leary (Dental Cosmos, 1910, vol. iii), after 
three year's experience in the use of bacterial 
vaccines, began an investigation of pneumo- 
bacterin in pneumonia. An appeal was made 
to several medical groups to test the value of 
bacterial therapy. The total number of cases 
was 83, eight patients died (9.7 per cent.) 
\ usual death rate, from 20 to 25 per cent.) ; 
34 of the cases occurred in alcoholic pneu- 
monia, 6 of whom died (17.7 per cent.). Previ- 
ous death rate from alcoholic pneumonia, 41 
to 53 per cent. In 8 cases the crisis occurred 
on the third day. 

The author advises the early administration 
of pneumo-bacterin. The bacterin treatment 
should be employed "the moment a diagnosis 
is established. A full dose should be injected 
of from 10 to 50 million, progressively increased 
in acute cases, every 4 to 8 hours." 



THE HYPODERMIC SYEINGE. 159 

Morgan (Pro. Koy. Soc. of Med. vol. iii, No. 
9, Sup. p. 5) treated 43 cases of pneumonia 
with pneumo-baeterin (some of the cases were 
treated with stock bacterin and some with 
autogenous). In many of the cases he admin- 
istered doses of 50 million of the autogenous 
bacterin without any harm, but he believed that 
doses of 15 million to 30 million would usually 
give the best results. In the cases reported 
where an artificial crisis was not produced the 
temperature fell by lysis with marked improve- 
ment in the symptoms. Morgan points to one 
of the most noticeable features as being an 
improvement in the general condition even 
without much change in the temperature. The 
patient is relieved, sleeps easily, and the appe- 
tite is improved. If there is a fall in tempera- 
ture soon after the bacterin is administered, 
which sometimes occurs in as short a period as 
one to two hours, another dose is indicated 
when the temperature rises again. If there is 
no change in twenty-four hours the dose should 
be repeated. He finds the opsonic index fre- 
quently unreliable as a guide to the progress 
of immunity in pneumonia. 

Harris (Br. Med. Jour. June, 1909, p. 1530) 
finds that a dose of 20 million to 50 million 
killed pneumococci may be given without harm, 
and is generally followed by a fall of tempera- 
ture within a few hours. The temperature 
usually rises again, but not to its previous level, 
and he found that it is necessary to repeat the 
inoculation several times. He advises the early 



160 THE HYPODEBMIC SYKINGE. 

use of the bacterin. He considers that every 
severe case of pneumonia should be regarded 
as possibly a fatal one, and suggests that the 
bacterin be employed as early as possible. 

Ager (L. I. Med. Jour. 1910, vol. iv) reports 
the case of a girl of nine who had been ill for 

19 days with lobar pneumonia. The circulation 
had been so bad that death seemed imminent. 
On the 20th day a mixed bacterin containing 

20 million pneumococci, 10 million staphylo- 
cocci, and 10 million stroptococci, was injected. 
A marked improvement was noticeable within 
a few hours. Two days later an increased in- 
jection (30 million pneumococci, 30 million sta- 
phylococci, 15 million streptococci) was given. 
The patient made a rapid and uneventful re- 
covery. 

Craig (Med. Rec. Nov. 18, 1911) reports 
treatment with pneumo-bacterin of 20 cases 
among old sailors, all over 60 (some 80-90 years 
old). Most were alcoholics, nearly all had 
chronic nephritis, arteriosclerosis, and dilated 
hearts. The average death rate in the institu- 
tion for the preceding five years from pneu- 
monia had been 66 per cent. Yet of the 20 only 
4 died, a death rate of 25 per cent., and of 
these 4 only 1 died directly from the pneu- 
monia, this being a very severe case of bilateral 
disease ; of the 3 other cases 1 was already com- 
plicated by purulent pericarditis, and another 
by acute uremia and acute dilatation of the 
heart. 

Sinclair (Med. Rec. Feb. 10, 1912) reports 



THE HYPODEEMIC SYRINGE. 161 

6 cases in which the first injection of pneumo- 
bacterin was given within 48 hours after the 
initial chill; one patient was an infant of 22 
months. Two cases in which the infecting 
agent proved on culture to be the pneumo-bac- 
illus of Friedlaender were not influenced. One 
of these went through the following course: 
Lobar pneumonia, appendicitis (operated) ; 
pleurisy (operated) ; alveolar abscess, arthritis, 
peritonitis, death from exhaustion, but with 
original infection. In patients treated later 
than 48 hours after the inital chill the disease 
was apparently unaffected, but no complica- 
tions developed. All recovered. 

Raw (Lancet, Mar. 9, 1912) reports 207 cases 
of pneumonia treated by pneumo-bacterin in- 
jection within two years, with a death rate of 
a little over 16 per cent. He emphasizes the 
fact that to be of real value the bacterin must 
be injected early in the illness; in fact, he 
states "if it can be used on the first or second 
day it acts at times almost miraculously.' ? 
After the fifth or sixth day when there is a 
general bacteremia the bacterin seems to exert 
little or no influence on the course of the at- 
tack. 

He thinks the usual dose of 10 million to 50 
million killed bacteria too small, and found 
that to get the full effect of the bacterin it is 
necessary to give larger doses. The practice in 
the cases treated was to begin with an initial 
dose of 50 million, followed in 24 hours, if 
necessary, by another injection of 100 million, 



162 THE HYPODEEMIC SYEINGE. 

and in some cases even 150 million were em- 
ployed. As a result of a large experience the 
author is convinced that the bacterin in itself 
is harmless, and he has never noticed anything 
but good effects from its use. In a certain 
proportion of cases it appears to have no effect 
either one way or the other ; on the other hand, 
in a great many cases injection of a large dose 
is followed by a feeling of comfort and relief 
associated with a rapid fall in the temperature. 
There is frequently a drop of one or two de- 
grees after a large injection of bacterin, but 
the temperature rises again, or until the trua 
crisis appears. It is apparently necessary that 
before the crisis occurs antipneumotoxin should 
be formed in the blood in sufficient quantity 
to neutralize the pneumotoxin. The effect of 
the bacterin on the pulse is always good, re- 
ducing it frequently in an hour by 30 to 40 
beats. 

Delayed Resolution — Coleman (Roy. Acad. 
Med. Ireland, Mar. 2, 1906) reported a case of 
unresolved pneumonia of 30 days' standing; 2 
injections of 45 million pneumococci, given at 
intervals of 16 days, brought about a complete 
resolution. 

Briscoe and Williams (Practitioner, 1908, p. 
675) conclude that in the more or less acute 
conditions following lobar pneumonia, the bac- 
terins cause marked improvement in the gen- 
eral condition. The effect of each injection is 
stimulating and the patient appears more 



THE HYPODERMIC SYRINGE. 163 

cheerful afterwards. In children the injections 
were followed by rapid increase in weight. 

Empyema. — Floyd and Worthington (Boston 
Med. and Surg. Jour. 1908) report 2 cases of 
pneumococcic infection treated with bacterins 
as follows : a girl of 2 years had complained of 
8 days of pain in the right side. The day be- 
fore admission to the hospital an abscess opened 
on the front of the chest and it was found ne- 
cessary to resect a portion of the eighth rib 
The child was weak and thin and in a preca- 
rious condition. As a culture from the dis 
charge showed pneumococci, a stock of bac- 
terin containing 500 million pneumococci was 
injected and 2 days later the opsonic index 
had risen from 0.6 to 1.17; the next day the 
index was 2.25 and the following day 50 mil- 
lion bacteria were injected. The child showed 
marked signs of improvement and was much 
stronger. Two days later 50 million were 
again injected, and after this inoculations were 
continued regularly. The child gained rapidly 
and after 3 \\ eeks was discharged from the hos- 
pital in excellent condition, the sinuses all 
healed. 

A boy 3^2 years old entered the hospital 
with a history of pneumonia followed by em- 
pyema. A portion of the eighth rib was re- 
sected and a collection of pus evacuated. Diag- 
nosis of pneumococcus infection. An injection 
of 50 million pneumococci was made and sim- 
ilar injections were continued every 3 days, as 
improvement followed every dose ; three weeks 



164 THE HYPODEKMIC SYRINGE. 

later the sinuses were almost closed and soon 
the child was sent to the country entirely 
cured. 

Septic Infection. — Betham Robinson (Br. 
Med. Jour. Mar. 13, 1909) reports a case of 
primary diffuse peritonitis caused by the pneu- 
mococcus and treated with bacterin. Owing 
to a diagnosis of appendicitis, the abdomen 
was opened and the localized abscess drained. 
A pure culture of pneumococcus was obtained 
from the pus, and five days after the opera- 
tion, as there was a rise in the temperature and 
in the pulse, treatment with bacterins was in- 
stituted. The patient received at intervals of 
five or six days, eight injections of ten million 
to 25 million pneumococci. After the first two 
injections there was a fall of temperature. 
The wound later became infected with stapyl- 
ococcus and it was necessary to make a coun- 
ter-opening for improved drainage before heal- 
ing occurred. 

Jowers (Practitioner, Sept., 1908) reports a 
case of peritonitis due to pneumococcus infec- 
tion of the tube; three injections of 50 million, 
60 million and 200 million respectively were 
given 8, 10 and 13 days after an abdominal sec- 
tion. The patient recovered, but the author 
believes recovery would have been more 
prompt if treatment had been commenced im- 
mediately after operation. 

Putnam (Bost. Med. and Surg. Jour., 1908) 
reports from A. E. Wright's clinic a case of ab- 
scess of the antrum of Highmore which was 



THE HYPODERMIC SYEINGE. 165 

caused by pneumococeus and was treated by 
the bacterin of this organism. Two inocula- 
tions at an interval of seven days resulted in 
complete cure. 

Arthritis Deformans. — Beebe and Medalia 
(Bost. Med. and Surg. Jour. 1908) report of a 
case of arthritis deformans in which the op- 
sonic index to various organisms was taken 
repeatedly. As the index to pneumococeus was 
always found to be low, they decided to experi- 
ment with bacterins of this organism. Stock 
bacterins were used, beginning with a dose of 
100 million. Soon afterward the pain disap- 
peared, although it had previously been neces- 
sary to keep the patient under the influence of 
morphine. They do not say how many doses 
were administered, but eventually the swellings 
about the joints were remarkably reduced and 
the patient was able to go about alone. The 
index rose above normal and remained high. 
They also report a case of mixed infection in 
which staphylococcus infection had been graft- 
ed on a pneumococeus infection, causing em- 
pyema in the right chest, which had been oper- 
ated on and drained a year before. The opsonic 
index was found to be low to both staphylococ- 
cus and pneumococeus. It was not possible to 
get a good growth from pneumococci secured 
from the patient and for this reason stock bac- 
terins were used. After three injections of 250 
million staphylococci and 100 million pneumo- 
cocci, the discharge had almost ceased. Dur- 
ing the next two months the doses were gradu- 



166 THE HYPODERMIC SYBINGE. 

ally increased in size to 1500 million staphyl- 
ococci and 250 pneumococci, and were given 
every two weeks. After one of these large in- 
jections, and presumably as a result of it, there 
was reinfection with a reopening of the sinuses 
and a free discharge of pus, the indices remain- 
ing above normal. The doses were, therefore, 
decreased to 250 million staphylococci and 100 
million pneumococci, and a few injections 
brought about a complete and permanent cure. 
Ulcus Serpens. — Allen (Practitioner, 1909, p. 
737) reports a series of cases in which bacterin 
treatment was successfully employed in dis- 
eases of the eye. Two patients with ulcus ser- 
pens of the cornea were among those receiving 
treatment. In one of these cases excision was 
apparently the only remedy. Despite the fact 
that the opsonic index was already 2.5, an in- 
jection of 250 million organisms was given. 
Within three days improvement began and 
three days later a similar dose was adminis- 
tered; 18 days after the second injection the 
index was 6.3 and the inflammatory process had 
quite subsided. In another case one eye had al- 
ready been removed for chronic ulcerative ker- 
atitis with shrinkage of the globe; 18 months 
later the second eye was attacked and grew 
steadily worse until vision was confined to the 
perception of a bright light; four injections 
were given, two of 200 million and two of 500 
million. Two months later the eye was free 
from inflammation and the vision improving, 
three other cases of the same nature which 



THE HYPODERMIC SYKINGE. 167 

seemed entirely hopeless were also treated with 
most satisfactory results. "The favorable re- 
sult obtained in these cases was largely due to 
the bacterin treatment, and but for it the first- 
mentioned patient would undoubtedly have lost 
his eye. ' ' Autogenous vaccines were employed 
in these cases. 

Allen (Vac. Ther. and Ops. Treat. Phila., 
1908) also reports three cases of perforating 
ulcer of the cornea with hypopyon, in which 
the eyes were apparently saved by the use of 
bacterins in doses of from 175 million to 600 
million. 

Pyorrhea Alveolaris. — Goadby (Lancet, 1909, 
vol. 1, p. 52) reports 47 cases of pyorrhoea alveo- 
laris treated with bacterins. Of these cases 36 
were cured ; that is all the general symptoms — 
anemia, toxemia, weakness and chronic intes- 
tinal dyspepsia — cleared up, together with the 
local suppuration. Nine of these cases were re- 
lieved ; that is to say, the general symptoms dis- 
appeared, although the local discharge re- 
mained. 

In taking cultures from the pus in order to 
determine which organism is the causative 
agent, he found the ordinary streptococci of 
the longus type. The pneumococcus was found 
at times, but streptococcus was more common. 
The micrococcus catarrhalis was commonly 
present, but probably was not the responsible 
organism. It was generally associated with 
streptococci or staphylococci. Constitutional 
disturbance rarely occurred after injection, but 



168 THE HYPODERMIC SYRINGE. 

in a few cases when the opsonic index was ab- 
normally low the first two or three injections 
were followed by vomiting, acute headache and 
general malaise. 

Leary (Dental Cosmos, 1910, vol. iii, p. 52) in 
an article on the bacteriology of pyorrhoea al- 
veolaris, states that he has studied about 100 
cases of pyorrhea, and has found a great vari- 
etj r of organisms. His most constant finding 
has been the pneumococcus, and he believes 
that Goadby's failure to differentiate this or- 
ganism was due to the fact that his primary 
cultures were made upon agar, on which the 
pneumococcus does not grow readily. The 
streptococcus longus and brevis appeared fre- 
quently. Staphylococcus was common, but 
usually associated with pneumococcus or strep- 
tococcus. The fusiform bacillus of Vincent 
was almost always present. This organism is 
a normal inhabitant of the mouth, and only 
occasionally become pathogenic. It is prob- 
able, however, that in many cases it is of im- 
portance in producing disease in individuals 
whose vitality has been lowered. 

As pneumococci and streptococci were found 
most frequently and the staphylococci were 
commonly associated with them, he has used in 
the bacterin treatment of these cases a stock 
pneumo-bacterin to which has been added a 
stock strepto-bacterin and often a stock sta- 
phylo-bacterin. The results are distinctly en- 
couraging in mild cases when pus was not abun- 
dant; in this treatment combined with the use 



THE HYPODEBMIC SYRINGE. 189 

of Lugil's solution locally it has repeatedly 
given perfect satisfaction. In pus cases it has 
ended almost equally well. When teeth are 
greatly loosened their perfect reestablishment 
in the socketing has been slow, and some teeth 
have had to be sacrificed. The healing of re- 
tracted gums and the obliteration of pus-pocket 
leave the joints between the gums and the teeth 
less perfect than they were originally ; that such 
joints will remain perfectly free from infection 
is almost too much to expect. 

Medalia (Bost. Med. and Surg. Jour., 1910, 
vol. clxii) has been experimenting for some 
time with the use of bacterins in the treat- 
ment of pyorrhoea alveolaris. He finds in 90 per 
cent, of his cases a pure pneumococcus infection 
with which staphylococci and streptococci are 
more frequently associated than other organ- 
isms. A large percentage of cultures taken 
from the gums of normal persons showed the 
presence of the same organisms as those found 
in the discharges from pyorrheal affections. The 
injury to the mucous membrane from concre- 
tions around the teeth renders it liable to infec- 
tion from these bacteria. The opsonic index was 
always found low to the pneumococcus, slightly 
low to the staphylococcus, and normal to other 
organisms. The injections ranged from 30 to 
150 million pneumococci, combined with from 
150 to 500 million staphylococcus aureus bac- 
terin. 

He has had 33 patients under treatment, 11 
of which are entirely cured ; five of these have 



170 THE HYPODERMIC SYRINGE. 

remained over a year without any recurrence. 
All of the others have shown great improve- 
ment, such as disappearance of pus, loose teeth 
becoming firmer, gums regaining their pinkish 
color and elasticity, and, when present, pain 
practically always relieved. Patients suffering 
from pyorrhea who are also troubled with 
rheumatic pains in the joints and muscles have 
shown great improvement in their rheumatic 
symptoms at the same time that their local con- 
dition has improved. 

Pneumococcal Vulvovaginitis. — Chappelle 
(Lancet, June 12, 1912) reports two cases of 
pneumococcal vulvovaginitis in children. Clin- 
ically the condition could not be distinguished 
from other forms of vulvovaginitis. 

The exact nature was recognized by bacterio- 
logical examination. The following treatment 
was employed: For a few days the child was 
kept at rest, and the parts bathed at frequent 
intervals with a warm antiseptic lotion. An 
autogenous bacterin of five million pneumococ- 
ci was given. The acute nature of the inflam- 
matory process rapidly subsided, and then 
warm vaginal douches of zinc permanganate 
were given under low pressure. 

The inflammatory process did not spread 
further than the vagina, and in ten days the 
discharge was almost gone, but pneumococci 
were still present in the vagina. Consequently 
another dose of vaccine of five million was giv- 
en and local treatment was continued. The 
condition cleared up rapidly, requiring only 



THE HYPODERMIC SYRINGE. 171 

four doses of vaccine in all. Had the patients 
been adults probably the external os should 
first have been plugged, to prevent possible as- 
cent of organisms during the douching process. 
Recently pneumococcal peritonitis has been 
found to be not at all uncommon in girls. To 
those believing that the path of infection may 
be an ascending one by way of the Fallopian 
tubes, these cases will be of interest. The im- 
portance of ascertaining the exact nature of the 
vaginal discharge should therefore be strongly 
emphasized. 

Antipneumococcic Serum. — Passive Immun- 
ization, or Serum Therapy. — When an infection 
has extended to numerous points beyond the 
original focus, and the bacteria or their prod- 
ucts are present throughout the blood and tis- 
sues (bacteremia, septicemia or toxemia), at- 
tempts artificially to induce the formation of 
antibodies may be unsuccessful. In these cases 
it is necessary to resort to the injection of the 
specific opsonins and other antibodies found in 
the blood of animals which have been actively 
immunized against the pathogenic organism 
causing the disease. This procedure is known 
as passive immunization, or serum therapy, and 
consists in utilizing in treatment the products 
of active immunization produced in a living or- 
ganism other than the patient. 

Antipneumococcic Serum is the blood serum 
of horses that have been highly immunized 
against the pneumococcus. After selecting a 
suitable animal, injections are made at pre- 



172 THE HYPODEKMIC SYRINGE. 

scribed intervals and in increasing doses of 
killed and attenuated living and finally viru- 
lent cultures of pneumococcus. This procedure 
is continued until a large number of living 
micro-organisms can be tolerated with but lit- 
tle reaction. The blood of the horse is then 
tested for antipneumococcic qualities, and if 
found sufficiently potent a large quantity is 
withdrawn. The serum is separated from the 
clot, standardized, and placed in containers for 
therapeutic use. As with the bacterins, the 
serum is polyvalent, i. e., in its production 
numerous varieties of virulent pneumococci are 
employed. 

Standardization. — The immunity unit for an- 
tipneumococcic serum, according to Neufeld 
and Handel, is established by ascertaining the 
amount of serum (administered subcutaneous- 
ly) necessary to protect a mouse from a subse- 
quent intraperitoneal injection, four hours 
later, of 10 to 100 times the lethal dose of liv- 
ing pneumococcic culture. A serum, 0.01 c.c. 
of which will secure this result, constitutes the 
standard (normal serum) by which the relative 
potency of other serum is estimated. 

Theoretical Consideration Relating to Cura- 
tive Serums. — Therapeutic serums may differ 
widely as to the qualities, potencies and the 
kinds of antibodies they contain. It is, how- 
ever, certain that this variation is dependent 
largely upon the nature of the antigen employ- 
ed in producing the antibacterial or antibody- 
forming reaction. To a great degree it is thus 



THE HYPODERMIC SYRINGE. 173 

subject to control. For example, if we employ 
bacteria themselves, while all the various anti- 
bodies are to a certain extent present in the se- 
rum, the principle antibodies produced are usu- 
ally opsonins, bactericidins, bacteriolysins, ag 
glutinins, etc. ; if only the toxic products of bac- 
terial metabolism are employed the antibodies 
predominating in the serum are chiefly of the 
nature of antitoxins, antiagressins, etc. 

It is thus readily seen that in the preparation 
of a therapeutic serum the chief consideration 
in the mode of attack of the particular bacteria 
against which the serum is to be employed. The 
diphtheria or tetanus bacillus, for example, sel- 
dom makes its way beyond the original point 
of infection in the throat, larynx, nasel pas- 
sages, etc., the serious manifestations of the dis- 
ease being due to the powerful toxin which is 
secreted or manufactured during the process 
of bacterial metabolism. In producing the an- 
tidiphtheritic serum or antitetanic serum, 
therefore, the toxin alone is employed as the 
antigen. With its repeated injection into 
horses they become immune on account of the 
antitoxin formed in increasing quantities after 
each injection and which remains present in 
the blood. The blood serum of the horse then 
constitutes the "diphtheria or tetanus anti- 
toxin," which has proved so efficacious in com- 
batting these infections. The diphtheria and 
tetanus bacilli themselves cause little harm and 
disappear in most cases a short time after the 
toxin has been neutralized by the antitoxin. 



174 THE HYPODEKMIC SYBINGE. 

The pneumococcus, on the other hand, forms 
practically no exotoxins (toxin formed in the 
process of bacterial growth), but multiplies 
rapidly and spreads throughout the tissues and 
even into the general circulation. It is not defi- 
nitely known whether the pathologic conditions 
produced are due to the absorption of toxic 
substances or the destruction of cellular tissues 
by the bacteria themselves, or to the poisonous 
action of endotoxins (toxins contained within 
the bacteria and liberated by the breaking 
down of the bacterial cells). It is, however, 
known that in resisting pneumococcic infection 
the body cells produce opsonins and other anti- 
bodies, and that the destruction of the bacteria 
is brought about by phagocytosis and bacterio- 
lysis. The methods adopted for the prepara- 
tion of antipneumococcic serum would, there- 
fore, be such as would produce the greatest op- 
sonic and bacteriolytic content; or, in other 
words, the immunization of the horse with liv- 
ing virulent bacteria. The serum of the im- 
munized horse consequently would have anti- 
bacterial properties in contradistinction to the 
antitoxic serums employed in the treatment of 
diphtheria and tetanus. 

A peculiarity to be taken into consideration 
when employing therapeutic serums is that their 
curative power apparently does not follow the 
law of multiple proportions. That is, a small 
dose of serum given in a mild infection may 
have absolutely no therapeutic effect; on the 
contrary, a large dose of the same lot of serum, 



THE HYPODEKMIC SYKINGE. 175 

given in a severe infection, will often place the 
patient on the road to recovery. This perhaps 
may be explained theoretically as follows: In 
a mild form of an infectious disease the lack of 
serious symptoms is probably due, not so much 
to the small number of bacteria or the small 
amount of toxins present, but rather to their 
lack of highly virulent characteristics or poi- 
soning qualities. In such cases the bacteria or 
toxins present would, however, absorb or com- 
bine with the antibacterial or antitoxic bodies 
injected with the same avidity as in the case of 
the more virulent infection. Thus a small 
amount of serum would be quickly neutralized 
without to an extent affecting the course of the 
disease. If, however, sufficient serum is given 
in a mild case to neutralize all of the bacterial 
products present, as well as to bring about a 
complete phagocytosis, recovery will ensue. In 
the same manner a severe infection may be suc- 
cessfully combatted by the injection of suffici- 
ent antibodies to neutralize all the toxins and 
to supply sufficient opsonins for the ingesting 
of the bacteria by the phagocytes. 

Dosage of Antipneumococcic Serum. — The 
dosage of antipneumococcic serum is from 2C 
to 60 c.c. every four to six hours for adults — 
children according to age — governed to a great 
extent by clinical observation. Probably no two 
cases are exactly alike in the natural resisting 
power of the patient, the virulence of the bac- 
teria, or the extent of the infection. As in the 
administration of diphtheria antitoxin the only 



176 THE HYPODEKMIC SYKINGE. 

safe rule would be to inject repeated doses of 
antipneumococeic serum until the crisis is 
passed or the infection shows a distinct ten- 
dency to recovery by lysis, a condition some- 
times resulting from the use of the serum as 
well as in natural recovery. The treatment 
should, of course, be continued until the patient 
is out of danger. 

Method of Administration. — The serum may 
be administered subcutaneously or intraven- 
ously. The modern trend of opinion, however, 
in the administration of all serums seems to 
favor the intravenous method, because large 
quantities of the specific antibodies may thus 
be brought immediately into contact with the 
pathogenic organisms or their toxins. When 
the serum is injected subcutaneously it is slow- 
ly, perhaps incompletely, absorbed into the 
general circulation, and its action is thus far 
weaker and more uncertain than when it is in- 
troduced directly into the blood stream. When 
a general septicemia or bacteremia is present, 
or when an acute infection has reached a seri- 
ous stage, only the intravenous method is held 
to be effective. For the same reason in pneu- 
mococcus meningitis, intradural injection 
would seem to be indicated. Experience with 
antimeningitis serum in cerebrospinal menin- 
gitis due to the diplococcus intracellularis men- 
ingitis has amply proved that injections of se- 
rum subcutaneously or even intravenously are 
of little avail when the spinal cord and men- 
inges are affected. 



THE HYPODERMIC SYRINGE. 17? 

Mode of Action. — In pneumonia due to pneu- 
mococcus antipneumococcic serum causes a 
much earlier occurrence of the crisis charac- 
terizing the disease. In a case of lobar pneu- 
monia folJowing the well-known classical 
course there is a gradual increase in severity of 
the symptoms culminating in a crisis on the 
seventh day of the disease. If antipneumococ- 
cic serum is injected early the crisis tends to 
occur about the third day and the symptoms 
are of less severity than in those in which 
serum therapy has not been employed. It has 
been observed that many of the usual compli- 
cations and sequels of pneumonia do not make 
their appearance is cases in which antipneu- 
mococcic serum has been administered. 

Clinical Reports. — Beltz (Deut. med. Woch., 
Jan. 4, 1912) records a series of 25 cases of lo- 
bar pneumonia in which injection of antipneu- 
mococcic serum was made intravenously within 
the period preceding the third day of the pneu- 
mococcic process, reckoned from the initial 
chill. The results were as follows: 400 units 
(Roemer's serum) were given as soon as diag- 
nosis was made. On the following day there 
was no improvement in the symptoms and a 
double dose was administered. In several seri- 
ous cases a third injection was given on the 
third day, and in a few, further injections were 
given during the course of the disease. The 
author compares these 25 with 25 similiar cases 
treated the year previously by the ordinary 
methods. In the latter series the crisis appear- 



178 THE HYPODEKMIC SYEINGE. 

ed on the seventh day in nine or 35 per cent., 
while in those receiving the serum treatment 
the crisis appeared on the third day in six 
cases, or 24 per cent, of the total. In those re- 
ceiving serum treatment the crisis appeared 
about the seventh day in 15 cases, in four, re- 
covery occurred by lysis, and four died. In 
two the crisis appeared on the ninth day. Of 
those who did not receive the serum treatment 
in all but two cases the crisis occurred on or 
about the seventh day of the disease ; three re- 
covered by lysis and four died. The author 
does not hesitate, therefore, to recommend the 
use of antipneumococcic serum in large doses 
given intravenously in the early stages of pneu 
monia, especially when a shortening of the 
duration of the disease is desirable. 

Rowland 6. Freeman (J. A. M. A., July 13, 
1912) reports a series of cases treated with an- 
tipneumococcic serum in which alternate cases 
were used as controls. The patients showed 
high temperature with good chest signs. There 
was no evidence of irritation at the site of in- 
jection and the serum was rapidly absorbed. 
The average of the children injected was 20 
months, the controls, 11 months. In a number 
of cases an immediate change in the appear- 
ance of the child followed administration of the 
serum. Patients that appeared septic previous 
to injection became brighter, of good color, 
took nourishment better and seemed much im- 
proved, although the condition in the lung was 
unchanged, and in some cases seemed to be 



THE HYPODERMIC SYEINGE. 179 

spreading. In some of the cases the serum in- 
jected appeared to have no results, but in the 
majority there seemed to be a better reaction 
on the part of the child after injection than 
before. 

Matthias Nicholl, Jr. (Ibid) says that after 
a fairly large experience with antipneumococ- 
cic serum with both children and adults, it 
seems that large doses of the serum should be 
employed, at least 100 c.c. In a recent attempt 
to immunize diphtheria patients against sec- 
ondary pneumonia there was apparently no re- 
duction in the death rate. It was difficult, 
therefore, to have a great deal of faith in the 
curative value of serum which had so little 
protective power against the organism which it 
was designed to combat. "In view of the fact 
that good results seem to follow the use of the 
serum in some cases, it is advisable to use it in 
prolonged cases which seem to be daily losing 
ground, but the dosage should be large. I have 
seen no bad effects from the administration of 
the serum even though the doses were very 
large. I prefer to give it intravenously, but 
100 c.c. may easily be given subcutaneously. 

Geronne (Berl. klin. Woch. Sept. 2, 1912) re- 
ports the histories of a series of cases of pneu- 
monia treated by antipneumococcic serum. The 
fact that the serum should be given early — 
within the first day or two of the infection, 
preferably intravenously in large doses — 20 to 
40 c.c. — is strongly emphasized. Persons so 
treated developed the crisis before the fifth 



180 THE HYPODERMIC SYRINGE. 

day. The serum seemed to have had little influ- 
ence on a course of disease after the sixth day 
of infection. In three cases in children the au- 
thor clearly demonstrated that the effect was 
not due merely to the foreign serum but to the 
antipneumococcic substances it contained. He 
injected normal horse serum and sheep serum 
and also antistreptococcic serum without any 
demonstrable effect. Serums should be highly 
polyvalent that is, include all strains of pneu- 
mococci obtainable. 



CHAPTER XI. 

Bacterins. 

(Continued) 

Pyocyano Bacterin. — Relative to the pyocy- 
ano-bacterin, the following is quoted from 
Working Bulletin No. 1, Third Edition, June, 
1911: 

The successful treatment of a case of pyemia 
due to this organism (Bacillus pyocyaneus) is 
recorded by Groves (Br. Med. Jour., May 15, 
1909, p. lib!)). There waa a history of hip- 
joint trouble dating back nine months. An op- 
eration was performed, and the head of the fe- 
mur and the socket found to be eroded. The day 
after the temperature rose to 103° F. and re- 
mained there for five days when it began to fluc- 
tuate three or four degrees, rising as high as 
104° P. Delirium, emaciation, multiple abscesses 
followed. Six weeks after operation the bacillus 
pyocyaneus was recovered in pure culture from 
the sanious discharge. A vaccine was made, 
and 40,000,000 given, without any appreciable 
result. Eight days later, when the temperature 
was 101.5° F., 60,000,000 were given. Within 
two days the temperature fell to normal and 
remained there. At, intervals of ten, fifteen 



IS* THE HYPODERMIC SYKINGtf. 

twenty-three and fifteen days, respectively, in- 
jections of 100,000,000 were given. From the 
date of the second injection the whole condition 
rapidly improved ; quiet sleep was secured, and 
food was well taken ; weight was put on rapid- 
ly and all the abscesses and sinuses healed, ex- 
cept one quite small superficial one. The sur- 
geon concluded that a more striking example of 
the potency of vaccine therapy could hardly be 
imagined. The bacillus pyocyaneus is fre- 
quently the offending organism in suppurative 
middle ear disease. 

Staphylo-Bacterin. — With the staphylo-bac- 
terin, as with all other vaccines of this charac- 
ter, that it is the indicated agent must be 
known, and this is determined through the use 
of the opsonic index. If the infection is not 
due to the staphylococcus, the staphylo-bacterin 
will prove ineffective, whereas, in the face of a 
contrary clinical diagnosis, as when the Neis- 
ser-bacterin fails, the staphylo-bacterin may 
give good results. It is imperative that proper 
diagnosis be made, either clinically, through 
the use of the laboratory determination of the 
bacteria present, or by use of the opsonic index. 

The staphylo-bacteria is frequently indicated 
in the treatment of acne, carbuncle, eczema, 
furunculosis, sepsis and gonorrhea, and is em- 
ployed as an immunizing agent to prevent in- 
fection. 

If the flow of blood is impeded through the 
associated ''brawny swelling,' ' the addition to 
the treatment of citric acid, or sodium citrate, 



THE HYPODERMIC SYRINGE. 183 

a dram three times a day, with local applica 
tions of sodium citrate to the infected area, will 
serve to overcome this obstacle and allow of the 
blood reaching the infected focus. 

Relative to the application of staphylo-bac- 
terin, and other data regarding it, the follow- 
ing is obtained from Working Bulletin No. 3, 
Second Edition, June, 1910: 

Dosage. — The proper dosage of bacterins is 
largely dependent on the nature of the case. 
The more chronic the case, the larger doses will 
ordinarily be required. The initial dose may 
vary from 25,000,000 to 250,000,000. It is gen- 
erally wise to start with a small dose and in- 
crease it according to the indications, basing 
the increase on the following points: After a 
proper dose there is a sense of well-being which 
lasts an hoar or two, followed by a sense of de- 
pression with increase of the local phenomina, 
the "negative phase". This should last a day 
or two and be followed by improvement, which 
should last from four to twenty days, the "posi- 
tive phase' \ If there is no negative phase, the 
dose is too small; if the negative phase is very 
severe or lasts more than three days, the doso 
is too large. The dose should not be increased 
as long as a negative phase follows each injec- 
tion, even although the bacterin has been used 
for a long time. Many clinicians make a prim- 
ary injection of 125,000,000 and if no negative 
phase occurs at the end of three to five days, 
they administer 250,000,000, to be followed, if 
there is no negative phase, at another interval 



184 THE HYPODERMIC SYRINGE. 

of three to five days by 500,000,000. Where a 
negative phase occurs, the dose previously used 
should be repeated. If the negative phase is 
severe, or lasts over three days, it is advisable 
to reduce the dose. Smaller doses should be 
used in acute and extensive infections. 

The site of injection is not of very great im- 
portance; but, when possible, it should be at a 
point from which the lymph drains through or 
past the local lesion. It has been suggested 
that bacterins be administered by the mouth, 
but not enough work has been done to establish 
their efficacy or dosage when administered in 
this way. 

Interval Between Doses. — The proper inter- 
val between doses must be decided for each 
case. In acute cases it will vary from two days 
to a week; in more chronic cases ten days to 
three weeks. If the opsonic index is taken, the 
second dose should be administered as soon as 
this falls to normal. If this is not used as an 
indication, the second dose should be given as 
the positive phase begins to decline, as shown 
by cessation of clinical improvement. 

Clinical Reports. 

Acne. — The results in acne have been very 
encouraging. The following papers may be re 
f erred to as typical : 

Dr. Ramsbolton (Lancet, 1907, Jan. 5) read a 
paper before the Manchester Pathological So- 
ciety in which he spoke of the use of staphylo- 
coccus bacterin in the treatment of furuncu- 



THE HYPODEBMIC SYBINGE. 



185 



losis and severe forms of acne. Mild cases of 
acne do not seem to yield so rapidly to the 
treatment. In the severe forms the opsonic in- 
dex was always found to be low to staphylo- 
coccus; in the milder forms this was not the 
case. 

Dr. Alex C. Soper Jr. (Chicago Med. Rec. 
1907, 105; 1909, Feb.) reports twenty cases, 
most of them of f urunculosis in infancy. A care- 
ful study of stock bacterins in comparison with 
autogenous bacterin shows little difference. Of 
five cases treated with autogenous bacterin all 
were cured and of fifteen treated with stock 
bacterin twelve were cured. He reports in out- 
line five of the cases, all of bad furunculosis, 
which were cured by an average of a little more 
than two injections. 

French (Br. Med. Jour. 1907, i, 256) reports 
the use of staphylococcus bacterins in the treat- 
ment of acne. He finds that it is of the great- 
est service and even in the worst cases brings 
about marked improvement in the complexion. 
After six doses at similar intervals, the erup- 
tions can be kept under with very little trouble, 
but it is best to continue the injections. In 
cases of long standing, in which there is indura- 
tion of the skin, Eberts and Hill (Am. Jour. 
Med. Sci. 1907, ii, 35) recommended the use of 
hot water applications for a period of twenty 
minutes daily, in connection with the injection 
of bacterin in order to draw the freshly opson- 
ized blood to the focus of infection. 

Inflammatory Skin Affections. — That the 



186 THE HYPODEEMIC SYRINGE. 

treatment is also effective in boils, carbuncles 
and other suppurative and inflammatory skin 
conditions, the following reports will show : 

Geo. W. Boss (J. A. M. A., 1907, ii, 1245) re- 
ports a series of cases treated by staphylococcus 
bacterin. He has treated boils, carbuncles, acne 
and septic wounds. In nine cases out of eleven 
the pain was relieved within forty-eight hours. 
Cases are likely to relapse, and for this reason 
injections should be continued after apparent 
cure. A large carbuncle was cured by one in- 
jection, which relieved all pain and tenderness 
within forty-eight hours. The results in sy- 
cosis have been very promising. 

Dr. Harlin, Chicago, reports good results in 
cases of sycosis as well as in those of acne. 

Wechselman and Michaelis (Deut. med. 
Woch., 1909, xxv, 1309) report that treatment 
of staphylococcus diseases of the skin with sta- 
phylococcus bacterins. They believe that it is 
a remarkably effective treatment. Only in ex- 
ceptional cases is it necessary to prepare an au- 
togenous bacterin, a polyvalent stock bacterin 
being ordinarily effective. Five cases reported 
in detail. 

Boehme (Deut. Arch, fur klin. Med., 1909, 
xcvi, Heft. 1) reports a series of cases treated 
with staphylococcus bacterins, and states that 
clinical improvement goes hand in hand with a 
rise of the opesonic index. 

Ohlmacher (J. A. M. A., 1907, i, 571 ; 1908, ii, 
571; Am. Jour. Sur. 1907, Dec.) reports a series 
of cases treated by bacterins, among which are 



THE HYPODERMIC SYRINGE. 18? 

the following cases of staphylococcus infection : 
He has treated two severe cases of acne vulgaris 
of one and two years standing with autogenous 
bacterin. In one case, after eight injections, 
nodules ceased to appear and seborrhea had giv- 
en place to a normal skin. In the other case, 
six injections have cured a most repulsive in- 
durated acne of the face. A case of impetigo 
was also treated with autogenous bacterins. 
The first injection brought the disease to a 
standstill and the second injection affected a 
cure. In a case of recurrent impetigo of four- 
teen months duration, two injections affected a 
cure. A two-year-old girl, in whom boils result- 
ing from infected mosquito bites had lasted six 
weeks, was cured by one injection. Two sim- 
ilar cases were cured by three injections each. 
Dr. Ohlmacher also reports a case in which fur- 
unculosis of the arm-pit was followed by sup- 
puration of the axillary glands and "it was 
clear that a total extirpation of the affected 
area would be necessary." The first dose of 
stock staphylococcus bacterin stopped the in- 
flammation, and a second dose resulted in the 
cure of the infected glands, with the exception 
of three, which had already softened and which 
healed promptly after evacuation. A very in- 
teresting case was that of a woman who pre- 
sented a dermatosis which covered a large part 
of the body and which was diagnosed as psori- 
asis. The condition had lasted eighteen months 
and the patient was confined to her room. A 
lesion was excised and planted on glycerine 



188 THE HYPODERMIC SYRINGE. 

agar. A growth of staphylococcus pyogenes 
aureus resulted, from which a bacterin was pre- 
pared and injected every seven days, cure re- 
sulting after five injections. 

Dr. Mark Richardson (Bost. Med. and Surg. 
Jour., 1908, clviii, 37) reports six cases of pus- 
tular acne which have been treated with sta- 
phylococcus bacterin with very marked im- 
provement. In two cases they were autogenous, 
in four they were not. The cases seemed to do 
equally well. He believes that greater success 
would be obtained if injections were combined 
with a bacterin from the bacilli acne. 

In a letter to the Lancet Dr. Geo. Wm. Davis 
(Lancet, 1909, ii, 958) reports a case of trouble- 
some eczema of the beard which had resisted all 
other treatment and spread to the external ear. 
He finally began the use of stock staphylococcus 
bacterin, giving injections alternately in the 
right and left forearms. He began with 100,- 
000,000 and increased to 500,000,000. Each in- 
jection caused a slight local reaction. After 
five injections the eczema of the beard had en- 
tirely cleared up and the trouble was confined 
to one ear. After the fifth injection (500,000,- 
000) a very acute pain, lasting two days, was 
experienced, the forearm became swollen and 
the temperature commenced to rise. For two 
nights the patient could not sleep. The injec- 
tion, however, was followed by a complete re- 
covery from the last remains of the eruption. 
He believes from this experience that an inter- 
val of one week between inoculations is unne- 



THE HYPODERMIC SYRINGE. 189 

cessarily long, and suggests that between doses 
of 100,000,000 he would first allow an interval 
of four days, and then one of three days, then 
an interval of two days. Between injections of 
100,000,000 and 250,000,000 he would allow four 
days, if possible. He usually uses three injec- 
tions of 250,000,000 with intervals of seven, six 
and five days, then an interval of ten days, fol- 
lowed by an injection of 500,000,000 and, if ne- 
cessary, continues inoculations of 500,000,000 
with intervals of ten days. He believes that 
bacterin treatment should be used in all cases 
of eczema which resist other treatment. 

In a later letter (Lancet, 190!), ii, 1382) Davis 
reports a case of eczema in a boy of sixteen, 
which was treated with staphylococcus vaccine. 
The entire face and anterior part of the trunk 
and thighs and legs were covered with the erup- 
tions, as were the flexures of the elbows, the 
front of the forearms and the palmer aspects 
of the hands and finders. The injections of the 
vaccine were all made in to the arms. Each in- 
jection was followed by local induration, and 
the next injection was given as soon as this in- 
duration disappeared. There was very little 
pain and no constitutional disturbance follow- 
ing the injection. The doses were from 100,000,- 
000 to 1,000,000,000. Nine injections were 
given in the course of six weeks, during which 
time the eruptions cleared up entirely except 
for a few scattered spots. 

Dr. R. T. Thorne (Br. Med. Jour. 1907, Feb. 
23) reports a case of furunculosis of three years 



190 THE HYPODERMIC SYKINGE. 

duration, in which he tried every ordinary 
method of treatment without effect. He finally 
used a staphylococcus bacterin, and after six 
injections the skin cleared up entirely and the 
patient has remained in perfect health. 

Dr. George Wolfshon (Berlin, kiln. Woch. 
1909, xlvi, 1017) reports a series of cases which 
he has treated with staphylococcus bacterins. 
He prefers the autogenous when these can be 
obtained, but recently he has secured very good 
results from the use of stock bacterins. He has 
abandoned the use of the opsonic index. He 
gives the inoculations every six to ten days, 
and believes that one must be careful in in- 
creasing the original dose. He has never given 
more than 250,000,000 staphylococci. He re- 
ports in detail five cases of furunculosis, all of 
which were treated with good results. A case 
of obstinate acne of the face and back, in which 
other treatment had been given without result, 
was cured by five injections. Three cases of pan- 
aritium were cured by from two to four injec- 
tions each. A case of large carbuncle on the back 
of the neck was entirely cured by four injec- 
tions. He reports one case of osteomyelitis of 
the tibia in which bacterin treatment was. used 
without avail. A case of puerperal mastitis 
was treated with good results. 

Maute (Wein. klin. Woch. 1909, xxii, 1083; 
Presse Med. 1909, 334) states that he has ob- 
tained good results in the treatment of furun- 
culosis by the use of staphylococcus bacterins. 
He believes that this treatment not only has- 



THE HYPODERMIC SYRINGE. 191 

tens the cure of the lesions, but is particularly 
effective in preventing the occurrence of new 
ones. 

Sellei (Weill, klin. Woch. 1909, xxii, 1485) re- 
ports 15 cases of furunculosis, 14 cases of sy- 
cosis, and 12 cases of acne, treated with bac- 
terins. The results in the cases of furunculosis 
and sycosis were almost always strikingly good. 
The cases of acne were much more stubborn and 
showed a greater tendency to recurrence, al- 
though the benefit obtained from the injections 
was usually noteworthy. The author believes 
that if the acne bacillus were used in connec- 
tion with the staphylococcus the results would 
be just as striking as those obtained in the 
treatment of the other diseases. In sycosis it 
is necessary to use local treatment in connec- 
tion with the bacterin treatment. 

Stubell (Muen. Med. Woch. 1909, lvi, 1152) 
has treated furunculosis, acne, sycosis, eczema, 
etc., with remarkably good results with sta- 
phylococcus bacterins. In discussing this ar- 
ticle, Galewski reports that he has had good 
results in the treatment of acne. 

Dr. Robert M. Merrick (Ann. of Gyn. and Ped. 
1908 210) has found the staphylo-bacterin useful 
in the treatment of "suppurative skin conditions 
complicating marasmus or malnutrition, such 
as furunculosis, pemphigus neonatorum, pustu- 
lar eczema and decubitus sores, which may vary 
from a slight abrasion to a gangrenous wound." 
The good results following staphylococcuc vac- 
cine in these conditions has led to its routine 



192 THE HYPODERMIC SYRINGE. 

use at St. Mary's Infant Asylum. The vaccine 
was used without determining the opsonic in- 
dex, and the amount used and the number of 
injections were governed solely by the clinical 
symptoms. He reports fifteen cases, most of 
them pustular eruptions, eczemas, boils or fur- 
unculosis. Only one case showed any bad re- 
sults following injection. In this case the sec- 
ond injection was followed by marked depres- 
sion and vomiting, which lasted a few hours. 
In twelve of these cases the treatment 
was followed by marked improvement. The 
improvement was not always permanent, 
and the author concludes that the num- 
erous instances of re-infection suggests the 
continued use of vaccine after the lesions have 
cleared up. The site of the injection seems to 
be entirely immaterial, and the injection is not 
usually followed by any local reaction. He 
suggests that the vaccine might be given by 
mouth instead of by injection. 

Theo. C. Beebe and Leon Medalia (Bost. Med. 
and Surg. Jour. 1908, clviii, 85) state that small 
doses of bacterin, so lonir as they produce a 
negative phase, arc of more benefit than in- 
creasing doses. When the injection no longer 
gives a negative phase, or the patient's condi- 
tion is at a standstill, an occasional large dose 
may be used for its stimulating effect. In 
cases of mixed infection inoculations of one 
bacterin will raise the opsonic index not only 
to the same bacteria, but occasionally to others. 
In cases of mixed infection the opsonic index 



THE HYPODERMIC SYEINGE. 193 

may be found low to several of the bacterin. 
In such cases we secure cultures of each organ- 
ism if possible, and inject bacterins from each 
separately, continuing to use that organism 
which brings about the greatest change in the 
index. When cultures show a growth of sta- 
phylococcus, a stock bacterin, made from five 
or six virulent strains, often gives better re- 
sults than an autogenous bacterin. The fol- 
lowing cases of .staphylococcus infection are 
reported. Two of furunculosis which had 

laste ral months each, and had shown a 

large Dumber of boils, were cured by re- 
stively five and eight injections. In one of 
these cases il was necessary to use the bacterin 
in rapidly increasing doses, as no negative 
Be occurred with small doses. Another case 
of furunculosis which had lasted three months 
cured by five injections, but two months 

r the boilfl began to appear, and two more 

injections were required to bring about perma- 
nent cure. In one ease of acne there was 
marked edema of the who >arm after each 

injection; the patient was subject to attacks 
of angio-neur< tic edema and the condition was 
not inflammatory. In addition, six cases of 
mixed infection are reported in which staphy- 
lococcus bacterin was used in connection with 
others. Three of these were cases of mixed 
staphylococcus and colon infections, two of 
staphylococcus and pneumococcus, and another 
mixed infection in tuberculosis. In each case 
the corresponding bacterins were used, and thp 



194 THE HYPODERMIC SYRINGE. 

result of the treatment in each case was favor- 
able. It was found in these cases that the re- 
action in the different patients to the same dose 
was even less regular than in the case of pure 
infection. 

Hartwell and Less (Bost. Med. and Surg. 
Jour. 1907, Oct. 17) have treated one hundred 
cases of staphylococcus infection with stock 
bacterin. The initial dose was 300,000,000 or- 
ganisms and the succeeding doses 600,000,000. 
The injections were given at regular intervals 
of four days until the lesions were cleared up. 
The authors regard this treatment as the most 
effective for boils and carbuncles. 

Nathaniel Potter (J. A. M. A. 1907, ii, 1815) 
points out the variations in the opsonic index 
caused by various affections, and in conclusion 
reports a few cases. Three cases of chronic 
facial acne improved rapidly after the use of a 
stock staphylococcus bacterin. A carbuncle 
of the neck was cured by two injections. 

Dr. Isadore L. Hill (Charlotte Med. Jour. 
1909, 231), Dr. Wm. H. Park (Bost. Med. and 
Surg. 1907, ii. 49), Dr. Arthur Whitfield (Prac- 
titioner, 1908, 697) Dr. A. Butler Harris (Prac- 
titioner, 1908, 657) Dr. J. H. Wells (Practition- 
er, 1908, 655), and many others also report good 
results from the use of staphylo-bacterins in 
the treatment of acne, boils and similar pustu- 
lar skin conditions. 

Septic Infections — The following reports are 
typical of those concerning septic infections: 

Gildersleeve and Carpenter (Arch, of Ped. 



THE HYPODERMIC SYEINGE. 195 

1907, 689) report a case of a boy nine years 
old, who had numerous abscesses in different 
parts of the body, followed by gangrene of the 
toes and bed-sores. An autogenous bacterin 
was prepared, and three injections resulted in 
the healing of all abscesses and almost a com- 
plete cure. 

Ross (J. A. M. A. 1907, ii. 1245) mentions, 
but does not report in detail, a case of a septic 
infection of the hand and one of orbital infec- 
tion, which were cured by the use of staphy 
lococcus bacterin. 

Christie (J. A. M. A. 1910, i, 705) states that 
he has had remarkably good results in the 
treatment of acute and chronic otitis media 
with injections of staphylococcus bacterin. He 
has treated 18 cases, 16 of which were perma- 
nently cured. In the other two cases three was 
dead bone, and though both patients improved 
under the use of the bacterin, they always re- 
lapsed when the treatment was discontinued. 
The first dose should be 125,000,000 increased 
to 250,000,000. The author concludes that "no 
one can treat by inoculation one of these ob- 
stinate cases of otitis media which refuses en- 
tirely, or only after prolonged treatment, to 
yield to local means, without reaching the con- 
clusion that bacterial inoculation is a power- 
ful agent for the cure of this disease. 

Rooker (J. A. M. A. 1910, i, 126) reports two 
cases of furunculosis and one of prostatitis, 
which were cured by injections of stock sta- 
phylococcic bacterin given in doses of from 



196 THE HYPODERMIC SYRINGE. 

100,000,000 to 400,000,000. The case of pros- 
tatitis was cured in six weeks, the injections 
being given every three days. This patient 
was also affected with pulmonary tubercu- 
losis, having a severe cough, and having had 
three hemorrhages. Within a week after the 
bacterin treatment was begun the cough was 
markedly improved and the patient's weight 
had increased eight pounds. This was, no 
doubt, due to the effect on a mixed staphylo- 
coccic infection. The cases of furunculosis 
were in children aged eight months and 
eighteen years. The first case was treated with 
doses of 5,000,000 repeated twice at intervals 
of seven days. The second case was treated 
with three injections of 100,000,000, 200,000,- 
000, and 300,000,000, respectively. No more 
boils appeared in either case after the bacterin 
treatment was begun. 

MacGowan (Cal. State. Jour, of Med. 1910, 
viii, 82) reports two cases of chronic cystitis 
treated with staphylo-bacterin. The first case 
showed a tendency to a septic condition, which 
suggested the use of bacterins. After four in- 
jections, at intervals of two days, the general 
condition cleared up, and there was no return 
of the septic trouble. The other case was very 
similar, the washings from the filtrate showing 
pure culture of staphylococcus aurous. The 
corresponding bacterin was therefore used in 
doses of 80,000,000. After two of these doses 
the temperature had fallen from 102.6° to nor- 



THE HYPODEBMIC SYKINGE. 197 

mal, and the septic condition which had pre- 
viously existed was entirely relieved. 

Ohlmacher (J. A. M. A. 1907, i, 571; 1908, ii, 
571; Am. Jour. Surg. 1907, Dec.) reports a 
case of pyelitis and several cases of middle 
ear infection cured by the use of bacterins. He 
believes that in tuberculosis there is generally 
a mixed infection and that it is, therefore, wise 
to combine the use of tuberculin with a bacterin 
of staphylococcus or other complicating forms. 
In suppurative syphilitic lesions it is also wise 
to combine specific treatment with the use of 
bacterins. Ohlmacher believes that the proper 
interval between injections is about a week. 
Another interesting case, reported by Ohl- 
macher, was that of palmer abscess, in which 
anti-streptococcic serum had been used with- 
out effect. An injection of stock staphylococ- 
cus bacterin prevented further extension of the 
inflammation and three injections of an auto- 
genous bacterin completed the cure, a small 
abscess being opened. 

Stubell (Deut. med. Woch. 1909, xxxv, 242) 
in an article on bacterin therapy, reports cases, 
most of which were skin abscesses, treated with 
staphylococcus bacterins, in which the results 
were very encouraging. In a case of puerperal 
sepsis, due to staphylococcus, the use of staphy- 
lo-bacterin did not save life, although improve- 
ment was noted after each injection. 

Dr. Lee (Bost. Med. and Surg. Jour. 1908, 
Jan. 2) believes that the opsonic index is of 
less value as an indication of the interval be- 



198 THE HYPODERMIC SYRINGE. 

tween doses than the clinical symptoms. It may 
be necessary to inoculate an extremely sick 
patient every twenty-four hours, while during 
convalescence every five days is sufficient. It 
is not enough to know that the infecting organ- 
ism is staphylococcus, the variety must be 
known. ±± case reported of septic inflammation 
of the finger, due to staphylococcus citreus, in 
which an aureus bacterin was without benefit, 
but prompt cure resulted from the use of the 
citreus bacterin. In a case of cervical abscess 
due to staphylococcus albus, inoculation with 
aureus was without benefit, but after two in- 
oculations with albus the patient was able to 
return to work. Dr. Lee believes that if we 
cannot determine the exact species responsible 
for the infection, the use of vaccines is inad- 
visable. 

Dr. Oilman Thompson (Asso. Am. Phys. 1909, 
May 11) reports a series of cases treated with 
bacterins, among which are the following: A 
boy, aged sixteen, was taken ill, with ulcerative 
endocarditis, two weeks before being brought 
to the hospital. Ten injections were given in 
the course of sixteen days. After this time the 
temperature remained normal and the patient 
was entirely cured of septicemia. The sec- 
cond case was an infection of the forearm, fol- 
lowing a burn on the hand. Septic pneumonia 
followed, and there was suppuration of the 
wrist, requiring incision. On the fifteenth day 
arthritis of the right knee-joint developed, on 
the nineteenth day pyonephrosis was dis- 



THE HYPODERMIC SYRINGE. 199 

covered, and on the twenty-seventh day a rapid- 
ly spreading abscess formed over the upper 
side of the chest wall and shoulder. The next 
day bacterin treatment was begun, and such 
prompt improvement followed that the sur- 
geons who had previously refused to operate, 
because they believed the patient could not live 
more than a few hours, opened the abscess on 
the shoulder and removed twelve ounces of 
pus. Four subcutaneous inoculations were 
given at weekly intervals, three of 100,000,000 
and one of 200,000,000. Immediately after the 
first inoculation the temperature, which had 
averaged 103°, fell to 101°, and the patient 
showed great improvement. Subsequent slight 
elevations were controlled by further injections, 
until, after two months of fever and one month 
from the first inoculation, the temperature re- 
mained normal and recovery was complete, the 
patient leaving the hospital with but moderate 
stiffness of the knee-joint. 

Floyd and Worthington (Bost. Med. and 
Surg. Jour. 1908, Jan. 2) report a case of facial 
carbuncle followed by angina and parotitis, 
successfully treated by staphylococcus bacterin, 
combined with administration of citric acid. A 
girl seventeen years old had a pimple on the 
right check, which was followed by inflamma- 
tion of the skin and carbuncle of the upper lip. 
She was unable to open her mouth and was 
somewhat delirious. Fifty millions stock sta- 
phylococcus was administered. Two days later 
a culture showed staphylococcus aureus, from 



200 THE HYPODEEMIC SYKINGE. 

which a bacterin was prepared and 25,000,000 
inoculated. Three days Jater definite improve- 
ment was noted and another injection of 25,- 
000,000 was given. The next day the blood 
was found to clot almost immediately upon 
being drawn, and for this reason, dram doses 
of citric acid were given for four doses. This 
resulted in a very marked improvement. The 
citric acid and bacterin treatments were con- 
tinued for four days, when the parotid gland 
became enlarged and painful. A further in- 
jection of 50,000,000 staphylococci caused a re- 
duction of the swelling and a gradual clearing 
up of the condition. The physicians believe 
that life was saved by the use of the bacterin. 

Dr. Hartwell (Mass. Gen. Hosp. Rep. xi, 1) 
reports from the Massachusetts General Hos- 
pital, good results in the treatment of localized 
staphylococcus infections, from the use of bac- 
terins. He uses an original dose of 300,000,000 
and continues with doses of 600,000,000 until 
cure occurs. In obstinate cases recurrence 
should be prevented by three or four injections 
given at intervals of a week after apparent 
cure. 

Dr. Helen Putnam (Bost. Med. and Surg. 
Jour. 1908, clviii, 15) reports a visit to Dr. 
Almoth E. Wright's clinic. She says that Dr. 
"Wright believes that in practically every local 
infection there is an obstruction of the blood- 
current, preventing sufficiently free access to 
the pathogenic bacteria. He therefore inocu- 
lates at a point where the newly formed opson- 



THE HYPODEEMIC SYEINGE. 201 

ins will drain through the diseased tissues on 
their way to the general circulation. For this 
reason he most frequently injects in the back 
of the shoulder when the trouble is in the face 
and head. A cumulative result cannot be ob- 
tained in the use of vaccines either by giving 
a dose before the effect of the previous one has 
passed off, or by giving progressively increas- 
ing doses, or by giving a larger dose because 
a smaller one has done well for some time. 
After the correct dose there is usually within 
an hour a wave of improvement, sometimes 
evident in the lesions, sometimes in the feelings 
of the patient. This improvement is brief, and 
during the following twenty-four hours or so a 
negative phase always occurs, with feelings of 
depression. After this the condition again im- 
proves, until by the third or fourth day the 
greatest improvement is reached, which is 
gradually receded from during the week. At 
the end of this period is the time to give a new 
dose. Dr. Putnam reports the following case 
of staphylococcus infection from Dr. Wright's 
clinic: A woman had run a splinter in her 
finger several weeks before and this was fol- 
lowed by many pustules on the back of the 
forearm. An injection of autogenus staphylo- 
coccus bacterin was administered, but the 
patient showed little improvement. A bandage 
was then wound around the arm and the result- 
ing congestion forced more lymph into the 
inflamed areas and also forced bacteria into the 



202 THE HYPODERMIC SYRINGE. 

blood current, producing anto-inoeulation. This 
resulted in improvement. 

As a Preventive of Infection — Pray (Edin- 
burgh Med. Jour. 1909) uses staphylococcus 
bacterins as a preventive of infection in surgi- 
cal work. He injects 500,000,000 staphylo- 
coccus and 150,000,000 to 250,000,000 strepto- 
coccus about one week before the operation. 
He believes that in this way, in some cases, he 
has prevented the occurrence of post-operative 
pneumonia. 

Tuffer (Presse Med. 1909, p. 689) speaks of 
attempts which have been made to prevent in- 
fection after operations. He states that he has 
had good results from the injection of killed 
cultures of staphylococci prepared according 
to Wright's method. 

Mixed Infection — Two abstracts will serve to 
show the advantages of using staphylo-bacterin 
in mixed infections. Dr. G. A. Grace-Calvert 
(Med. Rec. 1907, 327) advises the use of sta- 
phylococcus vaccine in association with tuber- 
culin treatment in cases of mixed infection in 
phthisis. 

W. M. Robertson (J. A. M. A. 1909, ii, 797) 
reports a series of cases of genito-urinary in- 
fections in which staphylococcus bacterin was 
used. He has obtained the best results in cases 
of chronic urethral discharge following gonorr- 
hea, but in which no gonococci were found. In 
cases due to staphylococcus he considers it al- 
most specific. He has used it in twenty cases 
of prostatitis and cystitis with a history of 



THE HYPODEEMIC SYRINGE. 203 

gonorrheal inflammation dating back from a 
few weeks to many years, and has not met with 
a case in which the subjective symptoms were 
not relieved by the third injection. If the in- 
jections are given every five to seven days with 
other appropriate treatment, the case goes on 
to complete recovery with surprising rapidity. 
The injections are probably of value in cases 
of scanty purulent discharge from the pros- 
tate, even when this is of long standing. In 
cases of cystitis following instrumentation or 
spinal lesions, the results have been gratifying, 
especially when the infection was due to sta- 
phylococcus. He reports six cases of gonorr- 
hea and prostatitis, and a case of very marked 
improvement in locomotor ataxia following in- 
jections for cystitis, but he is very conserva- 
tive about ascribing the good results in this 
case to the use of bacterin. He also reports a 
case of tuberculosis of the kidney which 
showed marked improvement under the use of 
staphylococcus bacterin and tuberculin. 

Robertson gives the injections every other 
day until after the third injection, then every 
five to seven days as long as they seem to be 
indicated. Only staphylococcus albus bacterin 
was used and always in doses of 400,000,000. 
He has given several hundred injections and 
has never seen an abscess follow one, nor had 
a complaint from pain or other bad effect. 



CHAPTER XII. 

Bacterins. 

(Continued) 

Strepto-Bacterin. Anti-Streptococcic Serum 

— As both the anti-streptococcic serum and 
strepto-bacterin are employed for treatment of 
like conditions they will, because of this fact, 
be considered under a single discussion. 

The serum is employed in the treatment of 
pyemia, puerperal sepsis, scarlet fever, ery- 
sipelas and mixed infections, while the bacterin 
is indicated in local infections, erysipelas, puer- 
peral sepsis, mixed infections, septicemia and as 
a preventative of scarlet fever and peritonitis. 

As to the clinical applications of anti-strepto- 
coccic serum, the following data is cited: 

PYEMIA. 

Yervant (Reforma Medica, Apr. 27, 1908) 
reports a case of pyemia following middle ear 
disease, which was treated with anti-strepto- 
coccic serum. The mastoid was opened, but 
without benefit. An injection of anti-strepto- 
coccic serum reduced the temperature to nor- 
mal in a few hours. Several injections were 
given, and although the patient was threatened 



206 THE HYPODEEMIC SYRINGE. 

with arthritis the recovery was without further 
trouble. In one patient, seventy-five years old, 
who was not operated upon, the temperature 
had risen to 106.7°, but after an injection of 
anti-streptococcic serum it fell to normal. When 
the serum treatment was suspended the patient 
rapidly grew worse, and finally died. 

Peabody (Med. Rec. 1908, i, p. 423) reports 
a case of cerebrospinal meningitis of strepto- 
coccic origin apparently cured by subdural in- 
jection of anti-streptococcic serum. Ten c.c. 
of the serum were given for the first dose, and 
repeated the second day, without benefit. The 
third day 10 c.c. of cerebrospinal fluid was 
withdrawn and replaced by 10 c.c. of anti-strep- 
tococcic serum. This was repeated at intervals 
of twenty-four hours, until four doses had been 
given. Two more doses were given at intervals 
of forty-eight hours. After the second injec- 
tion the spinal fluid was always found sterile. 
The temperature fell to normal, showing a 
slight rise each day for six days. Kernig's sign 
was present ten days after the other symptoms 
had disappeared. 

PUERPERAL SEPSIS. 

Bumm (Berlin, klin. Woch. Oct. 31, 1908) 
states that for the last ten years he has used 
an anti-streptococcic serum in the treatment 
of puerperal fever. In five cases of general 
septic peritonitis, as well as in four cases of 
post-operative peritonitis, the treatment was 
unsuccessful. In three cases of septicemia from 



THE HYPODERMIC SYKINGE. 207 

streptococcic endometritis two ended fatally 
and one recovered. In two cases with endo- 
carditis the serum was without benefit. In 53 
cases the serum treatment was begun early, 
while there was only septic endometritis. In 
each case streptococci had been detected micro- 
scopically. Thirty-two of these cases were very 
severe, and six of the patients died, one of 
peritonitis and five of pyemia. In 17 of them 
streptococci were found in the blood, and the 
author feels that 26 recoveries is a very good 
result. He finds that the temperature nearly 
always falls immediately after the injection, 
even in cases which end fatally, and there is 
distinct phagocytosis about twelve hours later. 
The appearance of leucocytes containing strep- 
tococci is direct evidence of the beneficial ac- 
tion of the serum. Bumm doubts whether the 
intravenous injection of the serum is entirely 
safe. 

Rothrock (Minn. Med. Jour. 1909, p. 632) 
reports the use of antistreptococcic serum in 
puerperal sepsis. The streptococcus pyogenes 
probably represents only one species, in spite 
of the great variability of its virulence. How- 
ever, serum prepared from an animal im- 
munized to several strains of organisms is more 
effective than that in whose preparation only 
one strain in used. The serum finds its greatest 
use in the early stages of infection and if used 
early it is certainly a very valuable agent. 

The author treated six cases of streptococcic 
puerperal infection with the serum, and in some 



208 THE HYPODEEMIC SYBINGE. 

cases the results were nothing short of brilliant, 
this being essentially true of cases in which 
the serum was administered within a few houvs 
of the initial chill. All six of these patients 
recovered, four of them promptly. The tem- 
perature falls a few hours after the first in- 
jection, but the fall is seldom pronounced until 
after the second or third doses have been given. 
The usual dose was 10 c.c. every twelve hours. 
As the serum is harmless, it would seem good 
practice to administer at least one dose in every 
case of puerperal sepsis with sudden onset, as 
the greatest benefit is seen when the treatment 
is begun early. If the treatment is not begun 
until forty-eight hours after the initial chill 
it is doubtful whether any benefit will be ob- 
tained. 

Leary (Intercol. Med. Jour. Austral. Nov. 20, 
1905) reports five cases of puerperal sepsis 
which were successfully treated with antistrep- 
tococcic serum. He gives 10 c.c. as the first dose, 
and repeats this two or three times within the 
first twenty-four hours. If the patient does 
not react properly the dose may be increased 
to 20 c.c. Unless the patient is seen early 
there should be no local treatment, as this does 
harm if the infection has spread above the 
uterus. 

Heynemann and Barth (Arch. fur. Gyn. 1909, 
lxxxviii, p. 1) report the use of antistrepto- 
coccic serum in puerperal sepsis. In vitro the 
serum did not possess as marked opsonic power 
as the serum of normal puerperal patients. The 



THE HYPODERMIC SYRINGE. 209 

results were not improved by the addition of 
either normal human or horse serum or by the 
use of horse leucocytes. The activity of the 
antistreptococcic sera is, however, not depend- 
ent upon their contents in substances which 
induce phagocytosis. Experiments on animals 
give the impression that the ordinary thera- 
peutic dose is too small. 

SCARLET FEVER. 

Young (Practitioner, Jan. 1909) speaks of 
the use of polyvalent anti-streptococcic serum 
in 75 cases of scarlet fever. In cases previous- 
ly treated without serum 22.6 per cent, showed 
marked inflammation of the tonsils. In the 
cases treated with the serum there was only 
2.6 per cent, inflammation. There were no 
cases of severe angina, and no suppurative 
cases. In one case there was gangrenous 
angina at the time the serum treatment was 
commenced, and this was favorably influenced. 
In cases treated without serum otitis occurred 
in 20 per cent. ; in those treated with serum in 
only 8 per cent. The occurrence of nephritis 
was not influenced. The acute stages of the 
disease appeared to pass over more rapidly in 
cases treated with the serum. As routine treat- 
ment in mild cases, 10 c.c. daily was used. In 
septic cases 20 to 40 c.c. were given two or 
three times a day. 

In 21 cases of diphtheria the anti-streptocic- 
cic- serum was used in combination with diph- 



210 THE HYPODERMIC SYRINGE. 

theria serum, and the results seemed to be ad- 
vantageous. 

Young (Br. Med. Jour. 1907, i, 745) reports 
a case of cervical abscess following scarlet 
fever, treated with anti-streptococcic serum. 
The abscess had been opened, and at the time 
the serum treatment was begun had been dis- 
charging for thirty-eight days; 10 c.c. of the 
serum was administered, followed by the same 
amount the second day. Two days later 20 c.c. 
were given. The following day there were only 
a few drops of pus on the dressings, and those 
were the last seen, and in four days the wound 
was absolutely united. A week later there was 
earache and mastoid tenderness and as it was 
feared that mastoiditis might follow, an injec- 
tion of 10 c.c. was given, followed the next day 
by 10 c.c. The following day the temperature 
was normal and the ear discharge was lessened. 
Five days later the discharge had ceased en- 
tirely and the child made an uneventful re- 
covery. It appears that in this case the anti- 
streptococcic serum put an end to a long stand- 
ing cervical abscess in a manner very short of 
wonderful, while later on it prevented a septic 
development in the mastoid cells. In both cases 
without creating any ill effects. 

Christison (St. Paul Med. Jour. 1906, Dec.) 
reports the use of anti-streptococcic serum in 
42 cases of scarlet fever all of which were of 
severe character, and in 31 of which strepto- 
cocci were found. There were four deaths. The 
treatment appeared to be beneficial. 



THE HYPODERMIC SYRINGE. 211 

Moltschanoff (Jarbuch fur Kind. 1907, lxvi, 
p. 503), during extensive experiments in Russia, 
found that the mortality in severe cases of 
scarlet fever was reduced from 47.6 to 16.1 per 
cent. Large amounts of the serum were re- 
quired. The temperature always fell after the 
use of the serum, and sometimes the pulse and 
respiration showed marked improvement, but 
this was not always the case. The duration 
of the fever did not seem to be influenced, nor 
were the throat lesions affected. The author 
states that unless the serum treatment is be- 
gun before the fourth day of the disease, it 
should not be used. 

Blacher (St. Petersburger Med. Woeh. 1909, 
No. 20) speaks of the treatment of scarlet fever 
with anti-streptococcic serum. He states that 
beneficial action is almost constantly shown by 
a striking improvement in the general condi- 
tion of the patient, a decided fall in the tem- 
perature, and an improvement in the condition 
of the throat, but these advantages are ob- 
tained only if the serum is used early in the 
disease. 

Compston (Br. Med. Jour. 1908, i, May 30) 
states that he has used the serum treatment in 
septic and severe cases of scarlet fever, with 
11 deaths in 37 cases. The previous mortality 
was very much higher. In very severe cases in- 
travenous injections seem to give more prompt 
relief than subcutaneous injections. Within 
forty-eight hours of the injection the tempera- 
ture began to fall and in another forty-eight 



212 THE HYPODERMIC SYRINGE. 

hours became normal. All involvement of the 
throat cleared up in most cases. The serum 
should be used early in the disease, in doses 
of not less than 50 c.c. This will produce a 
marked improvement in septic cases. 

Zuppinger (Wein. lklin. Woch. 1905, No. 44) 
states that he has employed anti-streptococcic 
serum in severe cases of scarlet fever. Of 139 
cases which he has treated in the last two years 
28 were considered severe enough to require 
the serum treatment. Of these 23 recovered, 
this being a much better result than was an- 
ticipated. It is of great importance to give 
the serum as early in the disease as possible, 
preferably in the course of the first three days. 
The serum was found to be the most valuable in 
cases of well marked pharyngeal involvement. 
The injection was usually followed by a fall in 
temperature of from one to four degrees. From 
100 to 300 c.c. of the serum were given, accord- 
ing to the severity of the case. In severe cases 
with simultaneous diphtheria the anti-strepto- 
coccic serum was combined with anti-diph- 
theritic serum. The author concludes that an- 
ti-streptococcic serum is the only remedy in 
the most severe cases. 

Robinson (Pediatrics, 1908, 384) reports five 
cases of scarlatina treated with anti-strepto- 
coccic serum, all of whom recovered. He con- 
cludes that the temperature and pulse fall in 
about thirty-six hours after the injection. Seri- 
ous cases are made mild. Complications are 



THE HYPODEEMIC SYEINGE. 213 

prevented or diminished. Convalescence is 
favored. 

ERYSIPELAS. 

Ayer (Med. Rec. Mar. 4 and Aug. 6, 1905) 
reports the results of 48 cases of erysipelas 
with antistreptococcic serum. He finds that 
the average duration of the disease was seven 
days, as compared to an average of nine and a 
half days in cases treated by other methods. 
There is a general improvement of the condi- 
tion of the patient, and the febrile albuminuria 
which is present in a large proportion of the 
cases is always diminished. The efficacy of the 
treatment is in direct ratio to the length of 
time which has elapsed between the onset of 
the disease and the first injection. 

Orton (Med. Age. 1906, p. 92) reports a bad 
case of facial erysipelas treated with anti- 
streptococcic serum. On two successive days 
20 c.c. were injected into the back, with no 
benefit. The next 20 c.c. were injected in four 
places immediately in advance of the line of 
demarcation, and this was repeated in the after- 
noon. The following morning the patient's 
temperature was normal and the swelling of 
the face had entirely disappeared. The author 
believes that in the treatment of erysipelas the 
serum should be injected in large quantities 
immediately in advance of the line of demarca* 
tion. 

Porneca (Bui. Gen. de Ther. Sept. 8, 1905) 
uses serum from patients suffering from ery- 



214 THE HYPODEKMIC SYKINGE. 

sipelas, in doses from 10 to 90 c.c. hypoder- 
mically. In nine cases which were treated by 
this method the headache and delirium disap- 
peared, the appetite improved, and the tem- 
perature fell after the injections. When al- 
buminuria was present it disappeared. He 
found that the serum does not possess any bac- 
tericidal power on the streptococci, although it 
may diminish their virulence. It exhibits an 
agglutinating power towards streptococci 
which is more marked in regard to organisms 
from erysipelas than from other lesions. Normal 
serum does not exercise any influence upon the 
course of erysipelas, but blood serum from the 
patient, heated to a temperature of 55 degrees 
C, and then re-injected, has the same effect as 
the serum of convalescents. 

Bouttiau (An. de la So. Med-Chir. de liege, 
June, 1906) reports results in the serum treat- 
ment of erysipelas in children. He considers 
the injection of anti-streptococcic serum the 
only rational treatment, and opposes the ad- 
ministration of internal remedies, with the ex- 
ception of an anodyne or a sedative. He ob- 
jects to the use of any ointment and simply 
dusts the surface with starch. The injections 
have had no bad effects, and they certainly re- 
duce the fever and shorten the disease. 

MIXED INFECTION. 

Roussel (N. 0. Med. and Surg. Jour. 1908, lvi, 
198) reports 12 cases of streptococcic infection 
treated with anti-streptococcic serum. Three of 



THE HYPODERMIC SYRINGE. 215 

the cases were bronchitis, with streptococci in 
the sputum, three were erysipelas, three scar- 
latina and three septic angina. In three of the 
cases there were rheumatic symptoms in addi- 
tion to the local infections. In all cases tho 
benefit from the serum was marked, and re- 
covery was obtained in each case. The dos<3 
was 10 c.c. repeated every four to eight hours. 
Bitter (Berlin, klin. Woch. 1909, xlvi, 634) 
speaks of the occurrence of streptococci in dis- 
eases of children, and of their treatment with 
anti-streptococcic serum. The streptococci do 
not often occur without the staphylococci in 
localized supperative processes, and in these the 
treatment directed against the staphylococci is 
of the greatest importance. The author has 
never found a pure streptococcic infection in 
tonsillitis, but in cases of malignant sore throat 
they were generally present. In 117 cases of 
articular rheumatism, streptococci were found 
in the tonsils thirty-three times. In 10 per 
cent, of the suppurative skin diseases, impetigo 
and pemphigus streptococci were demonstrated. 
In 100 cases of ulcerated stomatitis, strepto- 
cocci were found twenty-three times. The 
organisms were rarely found in enteritis or 
whooping cough. In diphtheria they are very 
commonly seen in conjunction with diphtheria 
bacilli. In scarlet fever they are evidently of 
great pathogenic importance. It has been only 
in mild cases that the organisms were not found. 
In erysipelas and infections of wounds they 
are always present. 



216 THE HYPODEEMIC SYEINGE. 

Twenty-two children with erysipelas in 
different parts of the body were treated with 
antistreptococcic serum, the dose being 2 c.c. 
per kilo of body weight. All these cases were 
under control by the second day, and 80 per 
cent, of them free from fever. The remainder 
were entirely free from fever on the third day 
of treatment. There were no disagreeable 
phenomena, except slight urticaria, which was 
not marked as that following the injection of 
diphtheria serum. In 87 cases which had been 
previously treated by other means, the shortest 
duration of fever was four days, and some of 
the cases lasted more than two weeks. In ad- 
dition to these cases of erysipelas, four cases 
of umbilical sepsis in infants were treated with 
serum. These were all far advanced, the 
patients all being very ill when they came 
under observation, and all four died. The serum 
is of greatest service in severe angina. Thirty- 
four cases of mixed infection of the throat with 
streptococci were treated. In all these cases 
there was rapid disappearance of the psuedo- 
membrane, and within thirty-six to forty-eight 
hours the temperature had fallen to normal. 
"Whoever has seen the threatening aspect of 
such cases will realize how good are these re- 
sults. In scarlet fever cases with the presence 
of streptococci, 19 cases were treated, with 10 
deaths, all 19 being very severe cases. In 14 
cases of septic diphtheria with streptococcic in- 
fection, the diphtheria serum was followed by 
the use of antistreptococcic serum, with ad- 



THE HYPODERMIC SYRINGE. 217 

vantageous results. All of these cases would 
probably have died under ordinary methods of 
treatment. Six of them recovered under the 
serum treatment. 

Smith (Med. Rec. 1904, i, p. 533) reports 
six cases of pustular smallpox treated with 
antistreptococcic serum; 20 c.c. were given 
at each dose, repeated every twenty-four hours. 
In these cases there was none of the general 
debility which followed the disease in former 
cases. The serum treatment shortens the 
course of the disease, prevents secondary in- 
fection, prevents pitting, and lessens the danger 
of lung and kidney involvement. If used early, 
the benefit is very striking. 

Cerrada (Muen, med. Woch. 1909, lvi, 198) 
speaks of the treatment of febrile tuberculosis 
with antistreptococcic serum. He has treated 
nine cases with such injections. In five cases 
there was no particular benefit. In three ad- 
vanced cases the sleep, appetite, and night 
sweats were favorably influenced. In an initial 
case there was apparently marked and lasting 
improvement from the treatment. In each case 
two injections were given. 

Boucheron (Uaz. Heb. de Med. et de Chir. 
June, 1898) uses antistreptococcic serum in 
the treatment of rheumatic iritis. He gives % 
c.c. the first day, and 1 c.c. on each succeeding 
day. In acute cases from three to six injec- 
tions are necessary. In chronic and long-stand- 
ing cases there is some improvement of sight 
and a more rapid absorption of exudates. The 



218 THE HYPODERMIC SYRINGE. 

serum exercises action on the streptococcus, 
and also acts as a stimulant to the nervous 
system in the same way as normal serum. 

Carrieu and Palen (Gaz. deg. Osp. e delle 
Clin. May, 1908, 607) report a case of a soldier 
attacked with severe influenza, complicated by 
symptoms of mengintis and pleuro-pneumonia. 
Streptococci being found in the sputum, four 
injections of antistreptococcic serum of 20 c.c. 
each were given with the result of completely 
subduing the fever, against which both quinine 
and antipyrin had proved inefficacious. 

Strepto-Bacterin — Local Infections. Gilder- 
sleeve (Mo. Cy. and Med. Bui. 1908, 607) states 
that local streptococcic infections, both primary 
and secondary to tuberculosis, are markedly 
benefitted by the use of strepto-bacterin. 

Beebe and Medalia (Bost. Med. and Surg. 
Jour. 1908, iii, 85) report a case of abscess in 
the neck due to the streptococcus, which was 
treated with strepto-bacterin. At the time of 
the first injection of 50,000,000 the patient was 
very weak, exhausted, pale, and emaciated, and 
there was considerable discharge from the 
wound. A week later the discharge had ceased 
and the wound was nearly closed. The patient 
had greatly improved in strength and appetite, 
and her color was good. Another injection of 
50,000,000 was then given, and a week later 
the wound was entirely healed, with no indura- 
tion around it. Four weeks later the patient 
had gained five pounds in weight, and was 
feeling perfectly well. 



THE HYPODEBMIC SYRINGE. 219 

Erysipelas — Harris (Practitioner, 1908, 647) 
reports a ease of erysipelas treated with strepto- 
bacterin. The inoculation was given on the 
sixth day of the disease, when the temperature 
was 105.4°, the pulse 140, the respiration 45, 
and the patient in imminent peril. This was 
followed by recovery by crisis, the temperature 
falling to 98.8°, fourteen hours after the in- 
jection. 

Duncan and Illman (N. Y. Med. Jour. 1908, 
ii, 552) report three cases of erysiplas treated 
by strepto-bacterin. The dose varied from 30,- 
000,000 to 60,000,000. The first case was one 
of facial erysipelas, in which a dose of 50,000,- 
000 streptococci was given on the sixth day. 
Twelve hours later the temperature fell, and 
from that time recovery was eventful. Previous 
to the injection being given, the lesion was 
spreading rapidly. 

The second case was also facial erysipelas, 
and the patient's condition was growing worse. 
On the third day of the disease an injection of 
bacterin was given, and by the morning of the 
next day the temperature was nearly normal 
and there was marked improvement in the con- 
dition of the patient, who felt so much better 
that he insisted on leaving the hospital. 

The third case was one of facial erysipelas 
following tonsillitis. The condition improved 
at first, but after it had existed for a week the 
inflammation began to spread rapidly. It 
spread continuously down the chest, reaching 
below the breasts, and on both arms. The 



220 THE HYPODEEMIC SYRINGE. 

temperature to 105.2°, and the patient was fre 
quently delirious. At this time strepto-bac- 
terin was given. The next day there was con- 
siderable fall in temperature. There was no 
further extension of the inflammation and on 
the third day the temperature was only a frac- 
tion above normal. The following day the 
temperature was normal, and from that time 
the recovery was uneventful. 

Schorer (Am. Jour, of Med. Sci. 1907, i, 728) 
reports 37 cases of erysipelas treated with 
strepto-baeterin. A study of the opsonic index 
shows that this rises until the third day of 
the disease and then gradually falls. Of the 37 
patients three died, these cases being compli- 
cated with some other disease in addition to 
erysipelas. On the whole, the course of the 
disease seemed to be shortened and the local 
condition was improved. The dose varied from 
25,000,000 to 100,000,000. Those receiving 25,- 
000,000 showed desquamation three days after 
the injection. Those receiving 100,000,000 des- 
quamated two and a half days after injection. 
The migratory form of the disease was seen in 
eight of these patients. The tendency toward 
this form of the disease was probably not in- 
duced by the injections. 

Ross (J. A. M. A. 1909, Mar. 6) reports the re- 
sults of treatment of 50 cases of erysipelas with 
strepto-baeterin. He believes that the treatment 
exercises a specific and controlling influence up- 
on the course of the disease, lessening its sever 
ity, preventing the spreading of the lesion and 



THE HYPODEKMIC SYEINGE. 221 

hastening recovery. The opsonic power of the 
blood was low during the acute process, while 
the infection was spreading. After the injec- 
tion of bacterin there was a rise in opsonic 
power, manifested clinically by the subsidence 
of malaise, mental restlessness or apathy pain, 
and tenderness, and by the localization of the 
inflammatory area. The author has frequently 
observed parallel series of events in bacterial 
inoculations for erysipelas, septic inflammation 
of the hands, and surgical tuberculosis. The 
evidence adduced in this connection was, he 
believed, sufficient to justify the use of baeter- 
ins prepared from the streptococcus in the 
treatment of erysipelas. In the first 16 cases 
of the 50 reported the opsonic index was taken, 
but as the clinical symptoms varied parallel to 
it, it was omitted in the other cases. In cer- 
tain severe cases a blood examination is ad- 
visable. It is unnecessary to prepare a bacter- 
in for each case, but it is advisable to have a 
complete stock bacterin made from several 
strains and as many cases as possible. An in- 
jection of 10,000,000 killed bacteria is given 
when the case is first seen; 20,000,000 is given 
if the case is not severe. At the second injec- 
tion the patient gets 10,000,000 more, if there 
has been any improvement. If no evidence of 
improvement follows, only 5,000,000 should be 
given at the second injection. In the less severe 
cases improvement is almost always manifest on 
the day after injection. The author then in- 
oculates with from 5,000,000 to 20,000,000 



222 THE HYPODERMIC SYRINGE. 

streptococci every second day until a week after 
the temperature has reached normal and the 
erythema has subsided. The rule is, "The more 
severe the case and the less satisfactory the 
clinical response the smaller the dose. "The 
site of injection was always chosen at a dis- 
tance from the inflammatory area. The results 
have always been so satisfactory that it has not 
been thought necessary to attempt inoculation 
near the site of infection. 

Puerperal Sepsis — Lloyd (Intercol. Med. 
Jour, of Austral, 1907) reports the following 
cases of puerperal sepsis, which were found to 
be mixed infections with staphylococci and 
streptococci and were treated with mixed strep- 
to-staphylo-baeterin. 

The first case showed a temperature of 105° 
and a pulse of 136 on the eighth day after de- 
livery. Cultures showed the presence of strep- 
tococci and staphylococci, and the injections 
were given of 25,000,000 streptococci and 250,- 
000,000 staphylococci. Seven injections were 
given, at intervals of two days, doubling the 
quantity at each injection. On the fortieth day 
the patient was sufficiently improved to leave 
the hospital. 

The second patient showed a temperature of 
103° and a pulse of 168. Two days later a cul- 
ture from the uterus showed the presence of 
streptococci and staphylococci. The uterus 
was swabbed with 2 per cent, formalin and 
packed with idoform gauze. As the patients 
condition continued to grow worse a bacterin 



THE HYPODEKMIC SYBINGE. 223 

was made and an injection of 100,000,000 cocci 
was given. From this time the progress was 
satisfactory, and the patient was soon convales- 
cent. 

Castler (Am. Jour, of Obst. 1909, 594) re- 
ports a case of puerperal sepsis treated by- 
mixed bacterins. The patient was admitted to 
the hospital three days after a miscarriage, with 
a temperature of 101° and pulse of 100. In 
spite of operation for the removal of pus tubes 
and energetic local treatment, the discharge 
continued to be very abundant. The abdominal 
incision refused to close, and a secondary oper- 
ation with posterior drainage was unsuccess- 
ful. During all this time the temperature 
ranged from 99° to 103°, and when the bac- 
terin treatment was commenced the patient was 
much emaciated and very anemic, with all the 
symptoms of chronic sepsis. Injections of 90,- 
000,000 streptococci and 150,000,000 staphylo- 
cocci were given every third day for four 
weeks. Almost from the first injection there 
was a noticeable general improvement in the 
patient. The temperature and pulse began to 
fall, and at the end of three weeks the temper- 
ature was normal. 

Mixed Infection — Vanderhoff (111. Med. 
Jour. 1909, 686) reports two cases treated with 
strepto-bacterin, and says that he knows of 
other cases in which it has been used with great 
benefit. These cases were both rheumatic iritis. 
The first case had had pain in the eye for seven 
days when an injection of 30,000,000 streptoeoc- 



224 THE HYPODERMIC SYRINGE. 

ci was given. Previous to this time the patient's 
condition had grown steadily worse. The day 
after the injection the patient felt better, and 
there was less pain. From this time there was 
rapid improvement, and in a few days he re- 
turned to his work. Soon after starting at 
work the eye became worse again, but after a 
second injection of streptococcic bacterin the 
iritis immediately quieted down, and has caused 
no trouble since. 

The second case was much the same, and the 
disease had also been in existence a week be- 
fore the first dose of 30,000,000 was given. The 
next afternoon there was a marked change for 
the better. The pericorneal injection was much 
less, and the patient could open his eye for the 
first time in several days. The case from this 
time recovered rapidly, only one injection being 
used. 

These two cases are simply examples of the 
good results which are frequently derived from 
the use of the bacterin treatment. The results 
have been particularly good in acute strepto- 
coccic and staphylococcic infections of the ear, 
nose and throat. The author states that his re- 
sults have been negative in chronic suppurative 
conditions of the sinuses, but is not able to say 
whether or not this is due to his not having con- 
tinued the treatment long enough. He con- 
siders the bacterin treatment very valuable, and 
thinks that the bacterins should be kept in 
the office of every physician, especially those 
in the country. 



THE HYPODERMIC SYKINGE. 225 

Williams (Am. Jour, of Obst. 1908, 152) 
states that strepto-bacterin has been used on a 
number of tubercular gland and joint cases, 
with the hope of influencing secondary infec- 
tion. Injections have been given in 35 cases 
of adenitis, in two of which there was a marked 
immediate improvement, with rapid recovery; 
and there was apparently some improvement in 
several other cases. In 15 joint cases, all 
showed improvement following the injections. 
In one case of peritonitis and arthritis, which 
had an absolutely bad prognosis, there was an 
immediate change for the better after the first 
injection, and the patient became convalescent. 
Although the cases have been too few to draw 
positive conclusions, the results have been very 
encouraging. 

Septicemia — Hartwell, Streeter and Green 
(Surg. Gyn. and Obst. 1909, ix, 271) state that 
they have treated 97 cases of sepsis with bac- 
terins. The initial dose varied from 5,000,000 
to 25,000,000, the dose being increased with 
each successive injection. The maximum 
amount given was usually 100,000,000. In each 
case an arbitrary interval of four days was 
made between inoculations. A bacteriological 
examination was made, and each case treated 
with staphylo-bacterin and strepto-bacterin, or 
with a mixed bacterin containing both strepto 
and staphylococci, according to the pathologi- 
cal report. In many cases antistreptococcic 
serum was used before the bacterin treatment 
was started but the results from the bacterin 



226 THE HYPODEBMIC SYEINGE. 

treatment were better on the whole, than those 
following the use of the serum ; 24 of the cases 
were general infections, 18 of these being puer- 
peral. All of the 18 cases recovered; 22 cases 
were septic abdominal wounds, and none of 
these were in bad condition at any time. In- 
fection was generally mixed, and correspond- 
ing mixed bacterins were used. A third group 
of 41 cases were all local sepsis, 25 of these 
being streptococcic infection. All recovered, 
some after extensive incisions. The fourth 
group does not include any cases of strepto- 
cocci infection. The author concludes that: 

1. Bacterial vaccines should be employed in 
cases of puerperal infection which do not re- 
spond promptly to routine treatment. 

2. Bacterial vaccines are especially useful in 
cases which have remained stationary for some 
time. 

Thompson (J. A. M. A. 1909, i, 1781) read 
a paper before the Association of American 
Physicians, May 11, 1909, in which he stated 
that he had treated seven cases of septic en- 
docarditis and one of pyemia with strepto-bac- 
terin, "with results which have demonstrated 
its effectiveness/' Three of the patients with 
septic endocarditis were cured, as was the one 
with pyemia. In several other cases of septic 
endocarditis there was evidence that the sep- 
tic process had been entirely controlled, al- 
though death ensued from such complications 
as tuberculosis or pneumonia. In none of the 
cases in which homologous bacterins were used 



THE HYPODERMIC SYRINGE. 227 

was there failure to produce improvement, such 
as fall in temperature. Several cases which 
came under treatment after months of illness in 
condition in which fatal issue seemed imminent, 
gave signs for many weeks of arrested pro- 
gress of the disease. The three patients who 
recovered from endocarditis had a type of the 
disease in which the author had never previous- 
ly seen recovery take place. The dosage of 
bacterin varied from 50,000,000 to 300,000,000 
at intervals of two, three and four days, ac- 
cording to the circumstances of the case. 

Farbach (Ky. Med. Jour. 1908, 688) states 
that he has used strepto-bacterin in one case 
of acute and one case of chronic streptococcic 
infection. The acute case was a septicemia, 
with a temperature of 105° and a pulse so 
rapid that it could not be counted. Within 
five hours after the first inoculation the temper- 
ature was subnormal and the pulse greatly im- 
proved. The patient eventually made an un- 
eventful recovery. The chronic case was 
characterized by groups of large carbuncles. 
After three inoculations all the lesions had dis- 
appeared, and the patient's general condition 
was greatly improved. 

Bristow (Med. Rec. 1908, i, 199), in a paper 
read before the Medical Society of New York, 
January 28, 1908, stated that he had used the 
strepto-bacterin in a series of cases, a few of 
which he reported. The first case began with 
an abscess of the superficial cervical glands, 
which was followed by phlebitis of the femoral 



228 THE HYPODERMIC SYRINGE. 

vein and septic endocarditis. This was followed 
by convulsions. After the first convulsion an 
injection of 5,000,000 strepto-bacterin was ad- 
ministered and the next day the temperature 
had fallen, but there was another convulsion. 
Eight days later an injection of 10,000,000 was 
given. From this time the patient steadily im- 
proved and soon recovered good health. 

The second case was admitted to the hospital 
with a diagnosis of acute rheumatism with 
acute endocarditis. A blood culture revealed 
the presence of streptococci. The patient re- 
ceived two or three doses of anti-streptococcic 
serum without benefit. Soon after, an injection 
of 5,000,000 stock bacterin was given. Two 
days later 5,000,000 were injected. From this 
time on the patient improved and recovery was 
uneventful. 

The third case was one of furunculosis, last- 
ing for two years. The streptococcus pyogenes 
aureus was isolated from the lesions. After the 
use of strepto-bacterin the condition cleared up 
and the patient remained free from furuncles 
for four months, when she had a single boil, 
which cleared up after the injection of bacterin. 

Van Cott (L. I. Med. Jour. Ed. 1909, 219) 
states that in cases of sepsis he formerly used 
autogenous bacterins because of the uncertain 
bacteriological nature of these cases. Recently 
he has used with equally good results a poly- 
valent bacterin, containing streptococci, sta- 
phylococci, and colon bacilli. This mixed bac- 
terin has proved of especial value in peurperal 



THE HYPODEBMIC SYKINGE. 229 

sepsis. It has the great advantage that no time 
is lost in the preparation of the bacterin. With 
the use of this bacterin the author feels that 
the prognosis is good in the majority of cases. 

Prevention of Infection. — Richard M. Smith 
(Bost. Med. and Surg. Jour., 1910, i, 242) re- 
ports in some detail the literature on the sub- 
ject of preventive inoculation of scarlet fever. 
He states that the first work which was done on 
this treatment for the prevention of scarlet 
fever was that of Steckler (Med. Rec. 1883, 
xxiii, 316), who, in 1883, injected the blood of a 
scarlet fever patient into himself and three 
days later had a scarlatina eruption, followed 
by desquamation. He then took desquamated 
scales from scarlet fever patients and injected 
them into healthy individuals. He found if the 
serum was later injected into such persons, no 
reaction was caused. 

The next work was reported in 1905 by Gab- 
ritschewsky (Russ. Vrach. 1905, No. 30), who 
obtained good results in the prevention of scar- 
let fever by the use of streptococcic bacterin. 
His work was based on that of Klein (Rep. of 
Med. Off. Loc. Brd. of Gov. 1885-86) and others, 
who had shown the importance of the strepto- 
coccus as the causative agent in scarlatina. Gab- 
ritschewsky claimed that after three doses of 
the bacterin — and usually after two doses — 
complete immunity was established against 
scarlet fever. This immunity is not complete 
until five to seven days after the last dose, al- 
though a relative immunity probably exists 



230 THE HYPODERMIC SYRINGE. 

from a week after the first injection. The im- 
munity lasts probably anywhere from six to 
eighteen months. Twenty-four hours after the 
first injection there appears at the site of inocu- 
lation an area of redness, which is slightly ten- 
der, and lasts from one to three days. Rarely 
there is some headache, or general malaise. In 
10 per cent, of the cases there appears an ery- 
thema over the body, resembling a very mild 
scarlatina eruption. After the second and third 
injections which are given at intervals of a 
week, there is usually no reaction. 

Smirnoff (Vrach. Gaz. 1909, xv, 368) used 
bacterin in thirteen small villages in Russia, 
where the sanitary conditions were very poor 
and where there was no possibility for quaran- 
tine. In the villages in which he used it no 
new cases were reported two weeks after the 
treatment was instituted, while in the other vil- 
lages the epidemic continued for upwards of 
two months. In these villages Smirnoff inocu- 
lated 127 children, of whom only five took the 
disease, three of these being infected before the 
second inoculation ; 91 children were not inocu- 
lated, and of these 36 were infected with scar- 
let fever, being about 40 per cent. Altogether 
he inoculated 455 persons, and among these 
there were only seven cases; five of these oc- 
curred after the first injection, two after the 
second, and none after the third. There were 
no deaths among the inoculated cases, as com- 
pared with 11 per cent, mortality among the 
uninoculated. 



THE HYPODEBMIC SYKXNGE. 231 

Yemelanoff (Vrach. Gaz. 1909, xv, 364) re- 
ports an epidemic in which eight or ten new 
cases were being reported every day and nearly 
every house in the village was infected. Quar- 
antine regulations could not be enforced; 610 
cases were inoculated and of these not a single 
one contracted the disease. It was possible to 
keep the schools open, even though the chil- 
dren came from infected houses. 

Dorofeyeff (Vrach. Gaz. xv, 366) reports the 
results in three small villages. He injected 142 
persons, two of whom took scarlet fever after 
the first injection. There were no cases after 
the second injection. These two cases were 
both very mild and without complications, al- 
though in the uninoculated cases 80 per cent, 
had nephritis. 

Zelikin (Vrach. Gaz. 1909, xv, 372) reports 
a severe epidemic in which there had been 210 
cases, with a mortality of between 30 and 40 
per cent. He inoculated 741 persons. Four 
had scarlet fever, all before the second inocu- 
lation. 

Markuzon (Prakt. Varach. 1907, vi, 292, 315) 
in 1906, inoculated all cases admitted into the 
hospital under his care, except those which had 
very high temperature, those showing ne- 
phritis, very young infants, and extremely de- 
bilitated cases. In patients with typhoid fever, 
pneumonia and other acute infections, the inoc- 
ulations had no effect on the course of the dis- 
ease, causing only a temporary rise in tem- 
perature. 



232 THE HYPODERMIC SYEINGE. 

Lifshits (Orakt. Vrach. 1907, vi, 773, 793) 
during a severe epidemic inoculated 170 cases. 
Only three of these took scarlet fever, all after 
the first inoculation. 

Nikitin (Russ. Vrach. 1907, vi, 989) inocu- 
lated 783 cases, among whom there were only 
eight cases of scarlet fever, all being in persons 
who had received only one inoculation. In the 
villages where inoculation was not practiced, 
16 per cent of the children had scarlet fever, 
while in the villages where it was practiced 
only 1.4 per cent took the fever. 

Akaparoff reports 308 inoculations, with 
three cases of scarlet fever, all after the first 
inoculation. 

Perwoff (Russ. Vrach. 1907, vi, 989) reports 
282 cases inoculated, only two of which took 
the disease, both after the first inoculation. 

Neurzoft inoculated 173 persons exposed to 
scarlet fever, and only two cases occurred 
among the series, both occurring the second 
day after inoculation. 

Schwarin (Russ. Vrach. 1907, vi, 891; Vrach. 
Gaz. 1909, xv, 367) inoculated 497 cases, only 
two of which subsequently took scarlet fever. 

Dobensky injected 132 cases, none of which 
took the disease. 

Langovoy (Centralbl. fur. Bakt. 1906, xlii, 
362, 463; Russ. Vrach. 1906, x, 565) inoculated 
all persons admitted to a hospital in Moscow, 
where during the four previous years three per 
cent of the children in the wards had had scar- 
let fever. Since the inoculation treatment, cov- 



THE HYPODERMIC SYRINGE. 233 

ering a period of several years, only four cases 
among 309 patients developed scarlet fever, a 
little over one per cent. 

From these published accounts it is evident 
that: 

1. The streptococcic bacterins have some in- 
fluence in controlling epidemics of scarlet 
fever. 

2. They should be given wider application 
in this country. 

Tuffier (Presse Med. 1909, p. 689) considers 
the use of streptococcic serum as a means of 
preventing postoperative infection. He says 
that the immunity produced by the use of se- 
rum is immediate, and reaches its maximum in 
twenty-four hours. Renne injected 10 c.c. 
three hours before operation for extensive ab- 
dominal cancers. In 12 operations, one patient 
showed suppuration, and one died of septic 
peritonitis. On the whole, it would seem that 
the method has less value than the use of bac- 
terins injected a few days before operation. 



CHAPTER XIII. 

Bacterins. 

(Continued) 

Typho-Bacterin. — Quoting from Working 
Bulletin No. 6, the following information is ob- 
tained : 

History. — The first work on inoculation 
treatment of typhoid fever was done by Frank- 
el (Deut. med. Woch. 1893, xix, 985) who pub- 
lished in 1893 an article on the treatment of ty- 
phoid fever with a killed culture of typhoid or- 
ganisms. Although his results were favorable, 
nothing further on the subject appeared until 
1896, when Pfeiffer and Kolle (Deut. med. 
Woch. xxii, 735) observed the production of 
antibodies following the inoculation of dead 
bacteria. 

Later in the same year, Wright (Lancet, 
1896, Sept. 19) published his first articles on 
the subject of anti-typhoid inoculation, and 
from that time on, articles flowed steadily from 
his pen. Being connected with the British 
army in India he was able to introduce the 
method of protective inoculation into the In- 
dian army, and his results showed the value of 
the method. 



236 THE HYPODEBMIC SYRINGE. 

In 1900 the Prussian War Ministry studied 
Wright's figures and came to the conclusion 
that the method was a very valuable one and 
should be introduced into the German army in 
the tropics. 

Jez (Wein. Med. Woch. 1899, xlix, 345) at- 
tempted to overcome the reaction which fol- 
lows inoculation by mixing his killed culture 
with a serum prepared from the glandular and 
nervous tissue of immunized animals. Palla- 
dine-Blandini (Hit Med. 1902, i, 746) separated 
the nuclo-proteids of the typhoid bacilli and 
used them for inoculation purposes. In the 
same year Besredka (An. de Tlnst. Pasteur, 
1902, xvi, 918) prepared an inoculation mater- 
ial by mixing a culture of typhoid bacilli with 
an immune serum and using the sensitized 
bacilli. 

Wasserman (Zeit. fur Hyg. 1892, xii) Neisser 
and Sheiga (Berlin klin. Woch. 1904, No. 4; 
Deut. med. Woch. 1903 No. 4) and Bassenge 
and Mayer (Deut. med. Woch. 1905, xxxi, 697) 
used filtrates prepared from typhoid cultures 
by special procedures. In this country Vaughan 
(N. Y. Med. Jour. 1907, i, 1170) showed that 
the typhoid bacilli could be separated into a 
toxic and non-toxic portion, and that inocula- 
tion of the latter had a certain protective 
power. 

Hesch and Kutscher (Klin. Jahrb. 1905, xiv, 
146) determined the protective powers of the 
toxins of Wasserman and Neisser-Sheiga, the 
methods of inoculation of Pfeiffer-Kolle (inocu- 



THE HYPODERMIC SYRINGE. 237 

lations of 1 oese, 2 mg., of an agar culture) 
and of Bassenge-Rimpau (2 injections of re- 
spectively 1-30, 1-15, and 1-5 oese at intervals 
of ten days) and the method of Wright. The 
protective powers of the Wasserman, Neisser- 
Shiga, and Bassenge-Rimpau methods were 
found to be insufficient. The constitutional re- 
action was much less marked, but the local 
phenomina were much the same as after the use 
of other methods. The effects of the Wright 
and Pfeiffer-Kolle methods were much the 
same in regard to reaction and protective pow- 
er. The protective power in each case was de- 
termined by the rise in the antibodies. Hetsch 
and Kutscher concluded that the Wright and 
Pfeiffer-Kolle methods were apparently equal 
in protective power, while the other methods 
are decidedly inferior. 

Summary. — It will be seen from these articles 
that the protection obtained by the inoculation 
of the various extracts of the bacilli is not as 
great as that obtained by the inoculation of 
killed cultures, and this method has, as a re- 
sult, been adopted almost universally as a 
method of choice. There is no longer any doubt 
as to the value of the injections as a means of 
protection against typhoid infection, and the 
severity of the reaction is not sufficient to dis- 
courage the use of the inoculations. The reac- 
tion is limited at the present time by injecting 
first a small amount, and ten days later, when 
the antibodies have appeared in the blood, in- 
jecting a larger dose which will give full pro- 



238 THE HYPODERMIC SYEINGE. 

tection. The value of the method has been re- 
peatedly demonstrated, both statistically ani 
by determination of the antibodies in the blood 
after inoculation. 

Vaccine Treatment. — Allen (Vaccine Ther- 
apy and Opsonic Treatment, Fourth Edition, 
1913, pp. 206-219) gives the following informa- 
tion relative to the vaccine, or bacterin, treat- 
ment of typhoid fever : 

Inasmuch as the portal of entry in this dis- 
ease is through the intestinal tract and the 
principal lesions are there situated, it is most 
conveniently considered now instead of in its, 
perhaps, more correct place among the septi- 
cemias. 

Bacteriology. — In view of the fact, which is 
becoming increasingly clearer, that a percent- 
age of cases, by no means inconsiderable is due 
to organisms other than the true B. typhosus of 
Eberth, exact determination should be made of 
the infective agent in all cases, whether vaccine 
treatment is contemplated or not. To the two 
varieties of organisms most closely allied to 
the B, typhosus, the names B. Paratyphosus A 
and B respectively have been given; to other 
varieties, which may give rise to conditions re- 
sembling typhoid fever in many respects, the 
title of ' paracolon bacilli' has been given, in 
virtue of a closer relationship to the B. coli 
communis. Although the primary lesions are 
situated in the intestines, a condition of septi- 
cemia is very soon established, and blood cul- 
tures yield a positive result in almost every 



THE HYPODERMIC SYEINGE. 239 

case after the first two or three days. The bac- 
teria disappear from the blood with some rapid- 
ity, so that by the end of the first week a much 
smaller percentage of positive cultures is ob- 
tained, even when large quantities of blood are 
utilized. Subsequently the bacteria may have 
to be isolated from the feces or urine. 

The organism so obtained is identified by 
means of its sugar reactions, and confirmation 
of its identity made by comparative serum tests 
with this organism and another known one to 
Which it is supposed to be similar. 

If an autogenous vaccine is prepared, it 
should be remembered that sterility must be se- 
cured either by heating at 53° C, but not over, 
for half an hour, and the addition of 0.2 per 
cent tricresol, or, as Semple recommends, by 
the action of 0.5 per cent carbolic acid alone, 
this being effective within twenty-four hours. 
If any greater degree of heat than 53° C. be 
employed, not only are the keeping properties 
impaired, but the immediate immunizing power 
is lowered. 

General Considerations. — * * * * the body 
elaborates various antibodies to the B. ty- 
phosus — viz., agglutinins, lysin, and opsonin. 
The relative importance of these bodies is not 
definitely known. Formerly the chief protec- 
tive role was ascribed to lysin; now the greater 
importance is assigned to opsonin and phagocy- 
tosis. By lysis the discharge is brought about 
of powerful endotoxins into the circulation, and 
it is to this cause that the continuous pyrexia 



240 THE HYPODERMIC SYEINGE. 

of the early stages of the disease is due. The 
intermittent temperature of the later stages is 
probably due in part to the absorption of other 
toxins from the ulcerated surface of the Peyer's 
patches, and in part to the liberation of endo- 
toxin which occurs when bacilli are dissolved 
before being ingested. The therapeutic use of 
powerful lytic sera may be fraught with danger 
owing to the liberation of excessive quantities 
of endotoxin; the therapeutic use of anti-endo- 
toxic sera may be found to modify the severity 
of the disease by neutralization of the endotox- 
in, and the therapeutic use of vaccines, by stim- 
ulating the formation of opsonin, may be ex- 
pected to influence the disease by bringing 
about the more speedy extinction of the bac- 
teria within the phagocytes, the endotoxins be- 
ing destroyed therein instead of being set free 
in the general circulation. Its good effects are, 
however, limited owing to the fact that in those 
situations where the bacteria are mostly stored 
(viz., spleen and Peyer's patches) there is ex^ 
haustion of the opsonin, and local conditions 
tend to nullify the effect of increased opsonin 
elaboration. It is also possible that ' comple- 
ment' may be in defect, and this we know not 
how to make good. 

Agglutinin probably plays a very subsidiary 
role, but, as we have seen, its amount is not de- 
void of prognostic import. The curves of ag- 
glutinin, lysin and opsonin, run a more or less 
parallel course, and inasmuch as opsonic index 
determinations are more than usually difficult 



THE HYPODERMIC SYRINGE. 241 

in this disease, the "agglutinin" curve is often 
substituted as a guide to the progress of im- 
munization. In the practice of vaccine treat- 
ment reliance is now, as a rule, placed for guid- 
ance on the temperature chart and the clinical 
signs and symptoms. 

Vaccine Treatment. — For a full account and 
discussion of the results obtained by himself 
and other observers, the reader should consult 
an article by Sir David Semple (Jour, of Vac- 
cine Ther. Feb. 1912). Papers by Stoner (Am. 
Jour, of Med. Sci., Feb. 1911), Callison (N. Y. 
Med. Jour., July 15, 1911), Watters and Eaton 
(Med. Rec, May 6, 1911), Makins and Forster 
(Can. Med. Jour., June, 1911), Smallman (Jour, 
of Roy. Army Med. Corps, vol. xii, p. 136), and 
Engelbach (Interstate Med Jour., June, 1912, p. 
537), will also afford useful information. 

The procedures adopted by each differs in re- 
gard to dosage and intervals. Thus Semple 
originally began with initial dose of 6,000,000 
to 50,000,000, but now recommends 100,000,000, 
this being gradually increased to 200,000,000 or 
300,000,000. These he gives daily or on each 
alternate day, according to the clinical re- 
sponse. He thinks that occasional estimations 
of opsonin and agglutinin are useful. Callison 
originally employed 25,000,000 but now prefers 
300,000,000, and employes estimations of op- 
sonin and agglutinin as a guide to the progress 
of immunity. He believes that negative phases 
after such doses are either non-existant or a 
negligible quantity. Meakins and Forster use 



242 THE HYPODEBMIC SYEINGE. 

1,000,000,000 as a first dose, 1,500,000,000 as the 
second about eight days after the first and 
2,000,000,000 as the third dose after a similar 
interval. Smallman, in his earlier eases, used 
100,000,000 as his first and second doses, the in- 
terval being nine or ten days. Later he used 
doses of 300,000,000 at shorter intervals with 
better results. Sadler (Jour, of Vacc. Ther. 
vol. i, No. 1, p. 17) prefers an initial dose of 
2,000,000, a second five days later of 1,000,000, 
this dosage and interval being continued sub- 
sequently. Alternatively he advocates doses of 
300,000,000. 

Summarizing the matured opinions of those 
who have had the greatest experience, it would 
appear that the best initial dosage is one of 
250,000,000 to 300,000,000, which may be safely 
repeated at intervals of three to five days, ac- 
cording to the immunizing responses and the 
clinical condition of the patient. 

There is some difference of opinion as to 
whether " stock" or autogenous vaccines give 
the best results. Some prefer a stock vaccine 
made from a strain such as we shall see is em- 
ployed for preparing the vaccine for antity- 
phoid immunization, viz., a long-cultured strain 
which has lost almost all pathogenic powers but 
still possesses a strongly immunizing action. 
Others prefer a polyvalent vaccine made from 
fully virulent strains, not only of the B. ty- 
phosus, but also of the paratyphoid bacilli. 
Others much prefer the autogenous vaccine in 
every case. Inasmuch as mixed infections by 



THE HYPODERMIC SYRINGE. 243 

the B. typhosus and a paratyphoid bacillus are 
not unknown and purely paratyphoid infections 
are fairly common, I think the wisest procedure 
is to employ for the first dose or two a stock 
polyvalent vaccine containing the B. typhosus 
and paratyphosus, proceeding meanwhile with 
the preparation of the autogenous vaccine and 
to utilize this for subsequent inoculations. 

The Results of Vaccine Treatment. — The im- 
mediate results of inoculation with a vaccine 
are best seen in the severely toxic cases. With- 
in twenty-four hours there should be, in the ma- 
jority of instances, a decided improvement in 
the general condition, a lowering of the tem- 
perature and pulse-rate, a clearing of the mind 
and evidence of greater comfort of the patient. 
A retrogression in any one of these directions 
is the signal for reinoculation. Occasionally 
improvement is delayed until the second day; 
in this case reinoculation may be deferred for 
two or three days, or until retrogression is ob- 
served ; but if no improvement is discerned by 
the end of forty-eight hours, the immediate ad- 
ministration of a double dosage is advisable. 
Treatment should be continued till the lapse 
of three or four weeks after complete deferves- 
cence, in order to secure the destruction of any 
bacilli which may still be lurking in the tissues. 

The observed influence of vaccine treatment 
upon the mortality and liability to relapse are 
best shown in tabular form on page 244. 

The number of cases so far recorded is too 
small to allow of a definite comparison being 



244 



THE HYPODERMIC SYEINGE. 



drawn between the results obtained by treat- 
ment with vaccines, and those obtained when 
treatment is conducted according to the usual 
routine principles. Both the mortality rate and 
the percentage of relapses vary greatly from 
time to time. The former varies between 10 
and 20 per cent., the mean of 15 per cent, being 
a fair average. Eelapses occur on the average 
in 20 to 25 per cent, of cases. The figures given 
below — viz., 4.1 per cent for the death rate and 
3.9 per cent, for relapses, would seem to leave 
a very appreciable balance to the credit of vac- 
cine treatment. 



Observer. 












^5 



di o 



<D to 

Ph o 



Semple 

Stoner and Callison 
Watters and Eaton 
Meakins & Forster 

Smallman 

Total 



60 


2 


2 


266 


12 


11 


36 




3 


41 


1 


1 


36 


3 




439 


18 


17 



3.3 
4.5 

2A 
8.3 
4.1 



3.3 
4.1 
8.3 
2.4 

3.9 



The unanimous opinion is that vaccines are 
quite innocuous when properly used, and that 
no aggravation or injury of any kind results 
from their use ; but that, on the contrary, they 
confer distinct benefits on the patient, by di- 
minishing the toxemia, shortening the duration 
of the disease, reducing the mortality and di- 
minishing the liability to relapse. 

Typhoid Carriers. — As the amount of study 
that is devoted to the elucidation of the causa- 



THE HYPODERMIC SYMNGE. 245 

tion of typhoid epidemics accumulates, the more 
increasingly clear does it become that in many 
instances such epidemics are initiated by con- 
tamination of the food and drink at the hands 
of those who prepare or supply it. These indi- 
viduals continually harbor the B. typhosus 
somewhere in their bodies, usually in the gall- 
bladder or kidneys and are accordingly known 
as "carriers". In the great majority of these 
a history of definite attack of typhoid fever is 
usually obtainable. As a rule, convalescence is 
uninterrupted, though perhaps rather pro- 
longed, and recovery apparently complete. The 
detection of these carriers is thus a matter of 
great concern. It is likewise one of no little 
difficulty owing to the fact, first demonstrated 
by Semple, that the discharge of bacteria may 
be very intermittent. It has been stated that it 
is impossible to declare with certainty that any- 
body who has recovered from an attack of ty- 
phoid fever has not become a carrier unless 
careful bacteriological examinations of the 
urine and feces, conducted at weekly intervals 
for at least one year, fail to detect the presence 
of the bacilli. Semple 's view that the storage 
of organisms takes place in the liver and kid- 
neys has been confirmed by numerous other ob- 
servers. Some of the investigations are of partic- 
ular interest. Alice Hamilton (J. A. M. A., Feb. 
26, 1910, p. 704) examined twenty-four persons 
with a history of gall-bladder trouble. Determin- 
ations of the opsonic index of the sera, after 
these had been heated at 58° C. for fifteen to 



246 THE HYPODEKMIC SYRINGE. 

twenty minutes, showed that seven out of the 
tw r enty-four had constantly abnormal indices to 
the typhoid or paratyphoid bacillus. Of these, 
those who had acute gall-bladder symptoms had 
a fluctuating index the others a persistently high 
one. All these seven individuals were proved 
to be carriers, five of a paratyphoid bacillus, 
two of the B. typhosus. In only five out of the 
seven was the Widal reaction obtained. Of the 
seventeen non-carriers, none had abnormal in- 
dex nor gave a Widal reaction in a 1 in 50 dilu- 
tion. Hamilton claims that index determina- 
tions are trustworthy and much simpler than 
bacteriological examinations of the urine and 
feces. 

It has occurred to me that much the simplest 
method of detection would be to do a "Cal- 
mette's reaction" on the eye using, not an emul- 
sion in water of the dead bacillus, as has been 
done for the diagnosis of active typhoid fever, 
but a preparation of endotoxin made by Mac- 
Fayden's method. In order to prove the relia- 
bility of this method, it will be necessary to 
make comparisons in a large number of cases, 
not only of those who are shown by direct ob- 
servation to harbor bacillus, but also those who 
have made complete recoveries. 

Although the liver and kidneys are the chief 
lurking-places of the B. typhosus, they are by 
no means the only ones. Thus Cammidge (Lan- 
cet, Jan. 19, 1909, p. 1739) records the detection 
of the bacillus in the stools of a case of pan- 
creatic glycosuria, a sufferer ten years previ- 



THE HYPODERMIC SYRINGE. 247 

ously from typhoid fever. In this ease the 
nidus would appear to be in the pancreas. The 
bacilli have also been recovered from bone ab- 
scesses, which have appeared long after appar- 
ently complete recovery from typhoid fever. 
Sir Hector Cameron (Br. Med. Jour. April 29, 
1911, p. 975) records one such case twenty- 
seven years afterwards. Other cases have been 
recorded six and ten years afterwards. It is an 
interesting question whether the routine treat- 
ment of typhoid fever, by means of vaccines, 
well into convalescence would not do much to 
diminish the number of these carriers, the exist- 
ence of whom is such a source of continual dan- 
ger to the whole community. 

Vaccine Treatment of Carriers. — Ordinary 
methods of treatment have proved entirely in- 
effectual in these cases, but in a few instances 
success has attended vaccine treatment. The 
first case to be so treated was reported by Ir- 
win and Houston (Lancet, Jan. 30, 1909, p. 
311). It was that of a carrier of seven years' 
duration, who was excreting large numbers of 
bacilli in the urine, but none in the feces. An 
injection of 50,000,000 produced rise of temper- 
ature, malaise and headache. Double this dose 
eight days later produced a milder reaction, 
and was followed eighteen days later by one of 
200,000,000. Two days after the third injection 
the urine was crowded with bacilli. The urine 
was rendered alkaline, and eighteen days later 
the B. typhosus had disappeared from the urine. 
Further doses of 300,000,000, 500,000,000 and 



248 THE HYPODERMIC SYRINGE. 

1,000,000,000, were given at intervals of four- 
teen days. The agglutination test was only ob- 
tainable then in the 1 in 10 dilution, instead of 
in one of 1 to 200, as formerly. There was con- 
siderable improvement in the general health, 
and the patient gained 10 pounds in weight. 
Although observations have been made of the 
urine for over two years, the B. typhosus has 
never again been detected. Houston (Br. Med. 
Jour., 1909, vol. ii, p. 1056) has since treated 
three more similar cases. In two of these com- 
plete cure appears to have been brought about, 
the other one has been markedly improved. 

Inasmuch as results equally successful with 
those obtained by Houston have been achieved 
by Dickson (Ulster Md. So., May 10, 1911) and 
other observers, it would appear that in vac- 
cines we have the only practical means of rid- 
ding "carriers" from their infection, though at 
times this treatment will also fail. 

Antityphoid Inoculation — Methods of Pre- 
paring the Vaccine. — The method approved by 
the Army Council for use in the British Army 
is as follows : A layer of broth, 1 to 1% inches 
in depth, is placed in special flasks of such form 
that maximum aeration is secured. The medi- 
um is inseminated with a special strain of the 
bacillus which has lost almost all its virulence, 
even for animals. Incubation is conducted at 
37° C. for thirty-six to forty-eight hours, when 
the growth is sterilized at 53° C. for one hour, 
sterility being observed by means of aerobic 
and anaerobic cultures, and 0.4 per cent, of ly- 



THE HYPODERMIC SYRINGE. 249 

sol is added to insure absolute sterility. The 
vaccine is standardized in the usual manner in 
duplicate. 

Semple advises that sterility should be se- 
cured without the aid of heat, and states that 
this is secured after twenty-four hours admix- 
ture with 0.5 per cent, carbolic acid. 

Castellani prefers a vaccine which has been 
heated to 50° C. for half an hour. This con- 
tains still living but greatly attenuated bacteria. 

Vincent advises the following procedure: 
The bacteria, which consist of typhoid and 
paratyphoid strains, are grown on a solid me- 
dium and removed therefrom and allowed to 
autolyze in 0.9 per cent sodium cloride solu- 
tion. The mixture is well centrifugalized, and 
the clear supernatant liquid removed, mixed 
with ether, and well agitated, the ether being 
removed by heating to 37° C. for a few min- 
utes. This vaccine is practically free of bac- 
terial bodies, and is a solution of endotoxins. 

The vaccine used in the English, French and 
American armies is prepared according to the 
first of these procedures; subsequent methods 
have been devised to improve the keeping prop- 
erties, as when the first method is employed 
it is found that the power to incite the forma- 
tion of opsonin, lysin, and agglutinin, begins to 
decline after three months, and falls off rapid- 
ly after six months. 

The Procedure of Immunization. — This varies 
slightly in different countries, and with differ- 
ent authorities. The present procedure in the 



250 THE HYPODERMIC SYRINGE. 

English army is to repeat the first dose of 500,- 
000,000 on the tenth day ; in the American army 
500,000,000 and 1,000,000,000 are given in suc- 
cession at intervals of nine days ; in the French 
army four doses are given. Inoculations are 
given subcutaneously either at a point of the 
upper part of the chest, at a site about 1% 
inches below the center of the clavicle; high up 
on the buttock, about 2 inches from the middle 
line ; or the side of the abdomen, about 2 inches 
inside the anterior superior spine of the ilium. 
Castellani, who formerly administered 0.5 c.c, 
1 c.c. and 1.5 c.c. of his vaccine at intervals of 
a week, now advises that a 500,000,000 dose 
of vaccine prepared according to the first meth- 
od should be followed a week later by 1 c.c. 
of his own preparation, and claims that thereby 
a higher degree of immunity is secured. 

Effects of Inoculation : 

1. Locally. — Tenderness begins to make it- 
self felt in live or six hours, and is at its worst 
in about eighteen hours, when there may be de- 
veloped redness over an area of two inches 
radius. Occasionally the lines of the lymphat- 
ics may be traced, and some tenderness of the 
corresponding lymphatic glands. These should 
all pass away within forty-eight hours. 

2. Generally. — Some degree of malaise is 
usually produced. In a small percentage of 
cases there is a tendency to f aintness ; occasion- 
ally a rigor comes on between the first and 
sixth hours; rarely there is diarrhea, vertigo, 



THE HYPODEEMIC SYKINGE. 251 

or a slight diffuse erythema. There is always 
a slight degree of pyroxia, usually to 100° F., 
occasionally to 101° F., and rarely to 103° F., 
which generally subsides by the end of twenty- 
four hours. 

Formerly it was stated that there was a 
marked reduction of opsonin, lysin, and agglu- 
tinin, in the serum for several days, followed 
by a greater rise. 

This "negative phase,' 7 which was formerly 
regarded as strongly contra-indicating immun- 
ization, either during an epidemic or when ex- 
posure to infection would occur within a few 
days, is now characterized by Leishman, Rus- 
sell, and others, as a pure bogey. Thus Leish- 
man points out that during a recent very se- 
vere epidemic at Maidstone, the attendants 
were all immunized at the time, yet not one 
contracted the disease ; also that typhoid is al- 
ways endemic in India, and that the garrisons 
are accordingly exposed to infection during im- 
munization, yet no epidemic is encountered. 

The duration of the immunity thus conferred 
has been studied by Harrison (Jour, of Roy. 
Army Med. Corps., 1907, p. 472) and others. 
They have found definite evidence of increased 
antibodies in the serum of men who had been 
inoculated as long as six years previously. 
Leishman believes that full immunity is main- 
tained for two years. 

The Results of Immunization, — Much discus- 
sion has taken place in the past as to the merits 



252 THE HYPODERMIC SYRINGE. 

of the procedure. Recent evidence is, however, 
greatly in its favor. For instance, during man- 
euvers of the American army at San Antonio 
the whole strength of 12,639 men were inocu- 
lated, with the result that only one mild case 
occurred during the whole four months, al- 
though among the populace there were 49 
cases and 19 deaths. Among a force of be- 
tween 3,000 and 4,000 who were encamped at 
Galveston, and received the same food, milk, 
and water supply as the inhabitants of the city, 
there was not one case of enteric. Among the 
inhabitants during the same time there were 
192 cases. During the preceding maneuvers in 
Florida, which were conducted at the same 
time of year and under precisely similar condi- 
tions, the water supply coming from an artesian 
well of accepted purity, 10,739 men, who were 
not inoculated, were engaged; 1,229 cases oc- 
curred, and 248 deaths; the significance of 
these figures is, however, in dispute. 

In India, as the proportion of the army vol- 
untarily undergoing immunization increases, it 
is noted that both the number of cases and of 
deaths show a steady and marked decrease; at 
the same time it must be admitted that the in- 
creased attention given to the " carrier " ques- 
tion cannot be without its effect. In the fol- 
lowing table are set out the rates of typhoid 
fever, and of deaths therefrom, and the ratio 
per 1,000 of men inoculated in the army of 
India from 1906 to 1910 inclusive: 



THE HYPODERMIC SYRINGE. 253 









Ratio of Men 






Death-Rate 


Inoculated per 


5Tear 


Typhoid Rate 


therefrom 


thousand 


1906 


15.6 


3.19 


66 


1907 


13.1 


2.77 


143 


1908 


14.5 


2.76 


225 


1909 


8.9 


1.58 


613 


1910 


4.6 


0.63 


823 



Thus the typhoid rate has fallen in five years 
from over 15 to under 5 per 1,000, and the 
death rate from over 3 to 0.63 per 1,000. Dur- 
ing 1910, among 70,000 men there was a total 
of 306 cases of enteric; 151 of these occurred 
in the 10,000 who were unprotected, and only 
155 in the 60,000 who were. Only 11.2 per 
cent, of the inoculated died, and 16.1 per cent, 
of the uninoculated. 

Finally, of the 16,496 men of the German 
army who took part in the Heroros campaign 
from 1904 to 1907, 7,287 were inoculated and 
9,209 not. There were 1,277 cases of enteric al- 
together. Among the inoculated the incidence 
rate was 5.09 per cent, and the death rate 6.47 
per cent. Among the uninoculated the inci- 
dence rate was 9.84 per cent, and the death 
rate 12.8 per cent. These various statistics must 
surely place the value of the proceeding be- 
yond all further question. 

Rabies Vaccine. — Although the process of 
immunization against rabies is not absolutely 
identical with that produced through the use 
of the bacterins, it is so similar in many ways 
as to place its discussion justly within this 
chapter. In his Text-Book on Pathogenic Bac- 
teria, Fifth Edition, 1907, McFarland gives a 



254 THE HYPODERMIC SYRINGE. 

full and concise description of the treatment 
of the disease, through the Pasteur method of 
immunization, and which is quoted as follows: 

For the cure of infected cases exactly the 
same treatment is followed as for the produc- 
tion of immunity. Indeed, the treatment of the 
disease is simply the production of immunity 
during the incubation period of the affection, 
so that the subsequent course is prevented. 
The patient, to be successfully treated, must 
come under observation early. The treatment 
consists of the subcutaneous injection of about 
2 grams of an emulsion of a rabbit's spinal 
cord which has been dried in a sterile bottle 
over caustic potash for from seven to ten days. 
The beginning dose is not increased in size, but 
each day the emulsion injected is made from a 
rabbit's spinal cord that has not been so long 
dried, until, when the twenty-fifth day of treat- 
ment is reached, the patient received 2 grams 
of emulsion of rabbit's spinal cord dried only 
three days and is considered immune or cured. 

This, in brief, is the theory and practice of 
Pasteur's system of treating hydrophobia. It 
is entirely in keeping with the ideas of the 
present time. When we remember that the 
first application of the method to human medi- 
cine was made October 26, 1885, six years be- 
fore the time we began to understand the pro- 
duction and use of antitoxins, it becomes one 
of the most remarkable achievements of medi 
cine. 



THE HYPODEEMIC SYKINGE. 255 

Frantzius (Centralbl. f. Bakt. u Parasitenk, 
May 12, 1898, xxii, No. 18) has studied the bile 
of animals immunized against rabies, and 
found it possessed of marked neutralizing ef- 
fect upon rabies poison, so that when 0.2 gram 
of bile and 0.2 gram of comminuted rabid rab- 
bit 's medulla are simultaneously introduced 
beneath the dura of a healthy rabbit, no dis- 
ease occurs. The bile of healthy oxen, sheep, 
hogs, etc., was also studied, but found it to be 
without effect. He concludes that the bile is 
the most powerful rabies antitoxin (?) yet dis- 
covered. 

The action of the bile in this combination 
probably corresponds with that discovered by 
Koch, who found that the bile of cattle suf- 
fering from the Rinderpest or South African 
plague, exerted an immunizing power by which 
healthy animals could be protected from the 
disease. 

Hogyes, of Budapest (Acad. des. Sci. de 
Buda-Pest, Oct. 17, 1897 ; Centralbl. f . Bakt. u. 
Parasitenk, 1887, ii, 579) believes that Pasteur 
was mistaken in supposing that the drying was 
of importance in attenuating the virus, and 
thinks that dilution is the chief factor. He 
makes emulsions of rabbit's medulla (1 gram 
of medulla to 10 c.c. of sterile broth) as a stock 
solution, to be prepared freshly every day, and 
uses it for treatment, the first dilution being 
1 : 10,000 ; then on succeeding days 1 : 8000, 
1 : 6000, 1 : 5000, 1 : 2000, 1 : 1000, 1 : 500, 1 : 250, 



256 THE HYPODEKMIC SYRINGE. 

1:200, 1:100; and finally the full strength, 
1:10. 

Oabot (Jour, of Exp. Med. 1899, vol. iv, No. 
2) prepared a stock solution of 8 parts of rab- 
bit's brain and 80 parts of glycerine and water. 
The quantity of glycerine added comprised one- 
fifth of the total bulk. After the emulsion was 
made it was filtered through sterile cheese- 
cloth. This emulsion containing the glycerine, 
if kept in the ice-chest, will be of standard 
virulence during the entire period of immun- 
ization. As the results of his experiments, 
Cabot found the dilution method attended with 
danger to the animal immunized, which is not 
true of the dried-cord method of Pasteur. The 
latter method is therefore the one to be pre- 
ferred. 

If an accurate diagnosis of rabies can be 
made, in cases where animals thought to be 
mad and have bitten human beings, by a sim- 
ple histologic examination, much time can be 
saved in beginning the Pasteur treatment and 
probably an increased number of cases saved. 

Anti-Rabic Serum. — The serum of animals 
that have received repeated injections of the 
crushed nervous tissue of rabid animals is neu- 
tralizing or destructive to the rabies virus in 
vitro, and is called anti-rabic. It was first 
mentioned by Babes and Lepp (Ann. de l'lnst. 
Pasteur, 1889, iii), who thought it exerted a de- 
pressive power upon other animals. Marie 
(Compt. rendu Soc. Biol, t, lvi, June 18, 1904, 
p. 1030) finds that this reaction is specific as 



THE HYPODERMIC SYRINGE. 257 

simple neurotoxic serum — i. e., serum of an an- 
imal given repeated injections of crushed nor- 
mal nervous tissue — is inert in its action upon 
the virus. The activity of the anti-rabic serum 
is also found to be in proportion to the virul- 
ence of the virus and quantity of the virus in- 
troduced into the experimental animal. 



CHAPTER XIV. 

Tuberculins. 

Relative to the various sorts of tuberculins, 
the following is quoted from Working Bulletin 
No. 1: 

Bacillen Tuberculin ("B E M ).— This is pre- 
pared by triturating or grinding the bacilli and 
suspending the same in normal salt solution. 
The germs are killed by this operation. The 
operation of grinding requires about two 
weeks. As there is still possible danger of liv- 
ing germs existing in the suspension. Bacillen 
Emulsion is usually rendered safe by the addi- 
tional process of heating the suspension for 
about one hour at 60° C. In either case it is 
preserved by % to 1 per cent, phenol or lysol. 
It therefore differs from a bacterin only in the 
fact that it is prepared from ground bacilli in- 
stead of whole bacilli. However, to all intents 
and purposes it is a bacterin. 

Tuberculin Ruckstand ("T R") or New Tub- 
erculin. — Koch in 1897 described the prepara- 
tion now known as Old Tuberculin, which he 
called "new" to distinguish it from his first in- 
troduction. "T R" is also prepared from 
ground bacilli but differs from Bacillen Emul- 



260 THE HYPODEEMIC SYKINGE. 

sion in method of preparation. The ground 
bacilli are treated with physiological salt solu- 
tion, centrifugated and the supernatant opal- 
escent fluid discarded, and the residue from 
this dried, ground, treated with physiological 
salt solution, contrifugated, and the clear super- 
natant fluid collected and retained. This pro- 
cess is repeated until all the residue is taken 
up. The clear centrifugates are united and pre- 
served by treating with glycerin to 20 per cent. 
This product is standardized so that 1 c.c. rep- 
resents the active substances found in 10 mg. 
of the dried bacilli. 

Old Tuberculin ("0 T").— This product is a 
glycerin extract of tubercle germs, and con- 
tains all of the soluble secretion products of the 
tubercule bacilli, in a 50 per cent, glycerin so- 
lution. It is prepared from pure cultures of the 
tubercle bacilli of five or six weeks' growth 
upon five per cent, glycerine bouillon. The cul- 
ture medium containing the germs is evaporat- 
ed by heat to 1/10 of its volume and filtered 
through porcelain to remove the germ bodies. 

Tuberculin Denys (Bouillon Filtrate) ("B 
F"). — This product consists of the filtrate from 
bouillon cultures of the tubercle bacillus and 
contains all the soluble products elaborated by 
the bacteria while grown on bouillon. It dif- 
fers essentially from Old Tuberculin in that no 
heat is used in its preparation and that it is not 
concentrated. 

Relative to the infections due to the Bacil- 
lus Tuberculosis and the application of the 



THE HYPODEKMIC SYBINGE. 261 

Tuberculins the following is quoted from Al- 
len's "Vaccine Therapy and Opsonic Treat- 
ment, Fourth Edition, 1913": 

Nature of Infection. — Sufficient evidence has 
now been accumulated to convince most minds 
that are open to conviction that the human and 
bovine strains of the tubercle bacillus are dis- 
tinct, though closely related, types. Just, how- 
ever, as there are intermediaries between the B. 
typhosus and B. coli, so there are intermediaries 
between the human and bovine types of the 
tubercle bacillus; but these are only rarely en- 
countered. While infection by the bovine type 
is quite common in young children, it becomes 
less and less common with advancing years, 
and I think it must be admitted that Spengler 
was wrong in attributing a very considerable 
percentage of cases of pulmonary tuberculosis 
to infection by the bovine type either 
alone or in conjunction with the human 
strain. Bovine pulmonary tuberculosis in 
adults would appear to occur in less than 
5 per cent, of all cases of phthisis. None 
the less there are certain definite advan- 
tages derived from employing highly poly- 
valent tuberculins, derived from both human 
and bovine strains, in the treatment of this dis- 
ease, and this procedure is the best alternative 
to the preparation and use of autogenous tuber- 
culin. 

Diagnosis of Tuberculosis. — In the early di- 
agnosis of tuberculosis lies the best chance of 
effecting a complete cure. To facilitate this 



262 THE HYPODERMIC SYRINGE. 

end numerous means have been devised, but it 
is quite impossible here to enter into a discus- 
sion on this point. Various clinical methods 
and observations may be employed, the help of 
X-rays sought, and such reactions utilized as 
those devised by Calmette and Wolff-Eisner, 
von Pirquet, Moro and Carle Woodcock. Here 
I propose to describe two methods only — one 
a comparatively new chemical method, which I 
have found to be of decided help in doubtful 
cases, the albumin test of Rogers ; the other, the 
oldest test of all, viz., the diagnostic use of Old 
Tuberculin which I agree with Bandelier and 
Roepke, Moeller, Fremuth, and others in re- 
garding as perfectly safe when properly em- 
ployed, and as giving by far the most reliable 
results of all. 

Roger's Albumin Test is performed as fol- 
lows : To 5 c.c. of the sputum 20 c.c. of normal 
salt solution and 5 or 6 drops of strong acetic 
acid are added. The mixture is well shaken 
and filtered and the filtrate tested for albumin 
by any of the usual ways — i. e., by boiling, the 
addition of nitric acid, potassium ferrocyanide, 
or trichloracetic acid. If the result is doubt- 
ful, a fresh portion of filtrate should be further 
diluted with 1 or 2 parts of the salt solution, 
and again tested. In order to secure reliable 
results the sputum must be fresh, and the in- 
clusion of saliva avoided as much as possible. 
Rogers, Buitron, Veresci and Lesieur, and Pri- 
vey have carefully observed the results given 
by this test, and have found: (1) that of cases 



THE HYPODEBMIC SYBINGE. 263 

without physical signs, which subsequently 
proved to be tuberculous, at least 75 per cent, 
gave a positive reaction; (2) that in all cases 
with tubercle bacilli in the sputum the result 
was positive; (3) that in miliary tuberculosis 
and pleurisy the result was not constant; (4) 
that cases of acute lobar pneumonia reacted, 
and that when the reaction persisted into con- 
valescence a new focus or a complication was 
indicated. Acute broncho-pneumonia and acute 
pulmonary edema were also positive. On the 
other hand, in acute bronchitis it was usually 
negative, in chronic bronchitis and in emphy- 
sema always so. In cardio-renal cases a posi- 
tive reaction was often seen. 

A positive reaction, therefore, indicated a 
pulmonary origin of the exudate, and excludes 
a bronchial source, and the more marked and 
constant the result the greater the likelihood of 
phthisis or pneumonia. 

My personal experience of the test is not ex- 
tensive, but this I can say, that in the few cases 
of doubtful pulmonary tuberculosis where phy- 
sical signs were almost absent, and tubercle 
bacilli not present in the sputum, and a positive 
reaction was given to the albumin test, subse- 
quent events confirmed the accuracy of the de- 
duction in each instance. 

The Old Tuberculin Test.— If a healthy indi- 
vidual receive an injection even so large as 0.01 
c.c. of Old Tuberculin (Koch), no symptoms 
beyond slight local tenderness will be exhib- 
ited. The case is very different with a person 



2te THE HYPODERMIC SYRINGE. 

afflicted with tuberculosis, especially if in an 
early stage. If the dose of tuberculin be ex- 
tremely small, no effect may be noted; if larger, 
a local hyperemia of the infected area; if still 
larger, a congestion; while if larger still, a 
constitutional disturbance of varying degrees 
of severity will result. If the infected areas be 
visible, as in the larynx or pharynx, the hyper- 
emia and congestion can be readily detected. In 
the lung there is an increase in the symptoms, 
confined to the area of infection; the auculta- 
tory signs are magnified and resemble a 
catarrhal condition of greater degree. Fine 
rales may appear where none were to be found 
previously or their number may be increased. 
Careful charting of the signs before and dur- 
ing the reaction is therefore necessary. 

It is possible to have this local reaction with- 
out any general one. If the latter be present, 
a few hours after the administration of a small 
dose of tuberculin the patient begins to feel a 
little nervous or tired, and perhaps has a heavy 
feeling about the limbs. With this there may 
be a slight rise of temperature of a fraction of 
a degree or a slightly accelerated pulse. With 
a larger dose the tired feeling and heaviness 
of the limbs becomes a true ache, which extends 
to the back and head, and the feeling is that 
of an on coming cold. With this the tempera- 
ture usually rises one or two degrees, and the 
patient may develop a cough where none was 
present before. If the dose be still larger, the 



THE HYPODERMIC SYRINGE. 265 

patient may have a rigor, and nausea and 
vomiting occur. 

The more experienced the physician, the less 
the amount of general reaction that he requires 
to establish a diagnosis, and an endeavor is 
made so to adjust the dose that a rise, at all 
events, of not more that 1° F. shall occur in 
temperature. If this be already above 100° 
F., the use of the test is contra-indicated, at all 
events, until rest and other appropriate means 
have reduced the temperature to the region of 
normal. 

Inasmuch as the reaction usually shows itself 
in from eight to twenty hours, the dose of 
tuberculin is best given at eight or nine o'clock 
at night, the temperature being then taken at 
six o'clock next morning and at two-hourly in- 
tervals. Examination of the chest for the local 
reaction should begin at the same time, and be 
repeated at three to four-hourly intervals until 
the presence or absence of local reaction is es- 
tablished. For the purpose of the test Koch's 
Old Tuberculin is usually employed. Some peo- 
ple being very sensitive to it, it is best to begin 
with a dose of only 0.0001 c.c, to which only 
very exceptionally is any response made. 
Should no reaction occur, the dose is increased ; 
0.001, 0.003, 0.005, 0.007, 0.01, 0.1 c.c. being 
used at successive intervals of two or three 
days until a positive result is secured, as is 
usually the case with the second or third of 
these doses in tuberculous cases. A negative 
result with the last of these doses is considered 



266 THE HYPODERMIC SYRINGE. 

to be final so far as infection by the human 
type is concerned. If thought desirable, infec- 
tion by the bovine type may be excluded by 
repetition of the test with bovine Old Tuber- 
culin (P. T.). Some cases of advanced phthisis 
do not respond to the test, but these present 
little difficulty in diagnosis. It has also been 
stated that certain cases of syphilis have given 
a positive reaction, but against this it must be 
borne in mind that sufficient proof that these 
cases were not also infected somewhere by the 
tubercle bacillus has not been always forthcom- 
ing. 

Contra-indications to use of the test are: (1) 
If the temperature rises above 98.6° in the ax- 
illa, or 99° F. in the mouth; (2) if definite 
signs of tuberculosis be present, if tubercle 
bacilli be present in the sputum, or if there has 
been a recent attack of hemoptysis; (3) if there 
be grave renal or cardiac trouble; (4) if the pa- 
tient be subject to epileptic fits. 

Immunity against the Tubercle Bacillus and 
the Tuberculin Reaction. — One attack of tuber- 
culosis does not seem to confer any immunity 
against another, but, on the contrary, rather 
to predispose to it — that is, if we except the 
immunity to subsequent infection by the human 
strain which appears to be conferred by an in- 
fection by the bovine strain. That general con- 
stitutional immunity, due probably to biochem- 
ical causes, exists is highly probable, but local 
immunity appears to be a most important de- 
fensive mechanism. 



THE HYPODERMIC SYRINGE. 267 

Phagocytosis apparently is a most important 
agency in the destruction of the bacilli, and is 
carried out almost entirely by the giant and 
endothelial cells. Whether the polymorphonu- 
clear leucocytes play any part therein, except 
perhaps in cases where the bacilli have gained 
access to the general circulation, is very doubt- 
ful. Opsonin, partly of the thermostable vari- 
ety, but chiefly of the thermolabile, can be de- 
monstrated in the blood-serum; but whether 
sensitization thereby of the bacilli is necessary 
prior to phagocytosis by the giant and endothe- 
lial cells has not been determined. 

Wasserman and others have demonstrated 
the presence of antibodies in those who have 
been immunized with tuberculin ; no bactericid- 
in or antitoxin has been demonstrated. Lysin 
and agglutinin are frequently present, but are 
sometimes absent even in cases that are doing 
well. 

The Tuberculin Reaction. — The exact manner 
in which the tissues of the tuberculosis subject 
react to an inoculation of tuberculin has been 
the source of much argument, and the matter 
of much investigation. The chief cause of dis- 
pute has been the delay which occurs in the 
response to the inoculation, a delay in no wise 
peculiar to tuberculin, but which is likewise 
experienced when any other vaccine is em- 
ployed. 

The recent work of Wasserman, Wolff-Eis- 
ner, Rosenau, Vaughan and Wheeler, and of 
others, has tended to show that in the tuber- 



268 THE HYPODERMIC SYRINGE. 

culous individual the cells are sensitized by the 
action of the infecting bacillus and its products, 
and that when tuberculin is injected it is split 
into a toxic and a non-toxic portion, the for- 
mer of these being rapidly bound by the sen- 
sitized cells and giving rise to the tuberculin 
reaction. In non-tuberculous individuals the 
condition of hypersensitiveness of the cells 
does not exist; when tuberculin is introduced 
into the tissues the splitting process into the 
two constituents is slow, the combination of 
cell and toxin either does not occur at all, or 
only to a slight extent, and the toxin is rapid- 
ly destroyed or discharged. When hypersensi- 
tiveness exists certain changes are produced in 
the cells whereby they are enabled to break up 
the tuberculin and combine it with great 
rapidity. 

Meyer and Schmitz have attempted to deter- 
mine what the substance is that reacts with the 
tuberculin. They infected rabbits with bovine 
tuberculosis, bled them, and allowed the serum 
to stand for twenty-four hours mixed with 
bovine bacilli, and then injected it into healthy 
animals; these became ill, with considerable 
rises of temperature and other constitutional 
disturbances. The serum from animals with 
advanced tuberculosis was found to answer 
best, and a still stronger reaction was obtained 
when washed blood corpuscles were used in- 
stead of serum. Also, when the washed blood 
cells of tuberculosis animals were allowed to 
react with tuberculin and saline solution, the 



THE HYPODEEMIC SYKINGE. 269 

mixture centrifugalized, and the saline solu- 
tion alone injected into healthy animals, a re- 
action was still obtained; this, however, was 
never the case when the blood cells or serum 
of healthy animals were employed. Heating 
above 65° C. did not destroy the bodies that 
gave rise to the reaction. 

It would thus appear that in the blood of the 
infected individual there circulates a substance 
combined for the greater part with the red 
blood cells, which combines with tuberculin, 
and is then capable of producing a f ebril reac- 
tion and other symptoms of disease in healthy 
subjects. 

Choice of Cases for Tuberculin Treatment, 
Choice of Tuberculin, Control of Dosage and 
Intervals — Results. — The decision as to wheth- 
er a given case of pulmonary tuberculosis is or 
is not suited for tuberculin treatment is a prob- 
lem by no means devoid of difficulty. The 
chaotic state into which the minds of all were 
thrown in the first place by the failures and ac- 
cidents encountered under the original system 
of dosage advocated by Koch, and in the sec- 
ond place by the disappointing results obtained 
by the application of Wright 's principles to the 
dosage of tuberculin in cases of pulmonary 
phthisis, has done much to impede progress. 
The better understanding that has been recent- 
ly attained of the nature of the tuberculin re- 
action and of the means whereby the body ac- 
quires immunity against the tuberculo-toxin 
on the one hand, and the bacilli themselves on 



270 THE HYPODEKMIC SYBINGE. 

the other hand, is serving to explain why it is 
that the small and infrequent dosage, so well 
adapted to the treatment of strictly localized 
and surgical tuberculosis is ill-adapted to the 
widely diffuse pulmonary form. In the for- 
mer variety autotoxemic disturbances are 
slight, and there is no necessity, therefore, to 
overcome sensitiveness, and establish a high 
degree of tolerance to the tuberculin toxin. In 
the latter condition, the autotoxemic disturb- 
ances, as evidenced by irregular pyrexia, 
quickened pulse-rate, and bad general condi- 
tions, are considerable; sensitiveness to the 
tuberculin toxin is then very high, and can be 
overcome only by establishing a high degree of 
tolerance by the administration of such doses 
of tuberculin as will rapidly nullify the admin- 
istration from within of irregular dosages at 
irregular intervals. It is at the same time ob- 
vious that the difficulty of establishing a satis- 
factory degree of toxin immunity will be min- 
imized by the adequate control of the inocula- 
tions of autotoxins, and that these latter may 
be so uncontrollable and so considerable as to 
render impossible the task of overwhelming 
their irregular impulses by the well-ordered 
waves of immunity set up in response to stimu- 
lation with regular and adequate doses of tub- 
erculin. The slight discord introduced into the 
performance of a piece of music by a flautist 
in a band may easily be masked beneath the 
greater volume of harmony emitted by the 
brass, but not all the sweet tones of flute and 



THE HYPODERMIC SYRINGE. 271 

clarionet and harp will mask the blatant dis- 
cords of trombone and double bass. Hence it 
is that phthisical cases in whom autoinocula- 
tion effects are marked are unsuited to tuber- 
culin treatment and that the control of these 
by rigid rest and other measures becomes a 
matter of such urgency and importance. 

The statement is frequently made that cases 
of mixed infection are unsuited to tuberculin 
treatment ; this is a very misleading statement. 
That cases of mixed infection are unsuited as 
a rule to tuberculin treatment is due, not to the 
fact that they are cases of mixed infection, but 
to the fact that autoinoculation effects are as a 
rule marked, and that, moreover, it is almost 
impossible to separate the autoinoculation ef- 
fects referable to the mixed infection from 
those referable to the tuberculous infection. 
The fact that mixed infection gives rise to in- 
creased cough and respiratory efforts has also 
to be borne in mind. These cases, therefore, 
are not intrinsically unsuited to tuberculin 
therapy ; they are so only temporarily, and un- 
til the mixed infection has been dealt with ade- 
quately according to the methods outlined in 
an earlier part of this chapter. There is a third 
class of case in which tuberculin treatment ap- 
pears to be contra-indicated ; i. e., that class in 
which sensitiveness to tuberculo-toxin is so 
great and tolerance so low that the adminis- 
tration of doses of tuberculin sufficiently great 
to overcome these disabilities is rendered im- 
possible by the grave constitutional disturb- 



272 THE HYPODEEMIC SYRINGE. 

ances thereby engendered. To this it may be 
urged that it is only the treatment of snch 
cases by massive doses of tuberculin that is 
contra-indicated, and that such cases are well 
suited to the small and infrequent dosages ad- 
vocated by "Wright. This may indeed be true, 
but in practice I have found it otherwise ; small 
infrequent doses do nothing to diminish sensi- 
tiveness and increase tolerance to the tuber- 
culin toxin, but have rather the contrary ef- 
fect; and the better practice in these cases is 
probably to place them under the best possible 
conditions, and leave them to establish toler- 
ance and diminish sensitiveness by means of 
controlled autoinoculations. This class of case 
is by no means common and it is to be expected 
most among the very early closed cases; occa- 
sionally such a condition is temporarily estab- 
lished by the administration of a diagnostic 
dose of tuberculin. Finally, in the following 
forms of the disease tuberculin treatment is 
liable to do more harm than good: (a) In the 
broncho-pneumonic form; (b) in those where 
caseation is marked, for softening, cavitation, 
and perhaps serious hemorrhage and dissemina- 
tion may be induced; (c) in those where the 
disease is very wide-spread, especially if the 
pulse be very rapid — i. e., 120 or over — a very 
rapid pulse is a much stronger contra-indica* 
tion than is a high temperature, for the latter 
is usually much easier of control than is the 
former; (d) serious complications. On the 
other hand, homoptysis, slight complications, 



THE HYPODERMIC SYRINGE. 273 

and pregnancy do not contra-indicate tubercu- 
lin treatment. 

Choice of Tuberculin. — With the general view 
that all tuberculins produce the same effect, 
and act in a similar manner and that one 
preparation brings about as good results as any- 
other, I cannot at all agree. While it is prob- 
ably true that the use of each and every tuber- 
culin tends to establish tolerance and diminish 
sensitiveness, it must surely be admitted that 
the use of such preparations as contain toxins 
only can never suffice to bring about an anti- 
bacterial immunity. Tolerance to tuber culo- 
toxin will enable the sufferer to go about his 
daily duties even though he continue to expec- 
torate great numbers of bacilli and perhaps 
suffice to minimize greatly the ill-results which 
would otherwise inevitably attend the bacteri- 
al infection, but it can never lead to its extinc- 
tion; this only a high antibacterial immunity 
can bring about. Granted that we know but 
little on this subject of antibacterial immunity, 
it may yet be reasonably deduced from analogy 
with every other variety of organism that the 
administration of the bacterial bodies and their 
essential protoplasm is the best available means 
for inducing its increase. When, therefore, 
toxemic symptoms predominate, it would ap- 
pear to be most rational to endeavor to stimu- 
late antitoxin formation by the administration 
of such toxic products as Old Tuberculin, P. T. 
0., or Bouillon Filtrate; in the more severe 
cases beginning with the mildest preparations 



274 THE HYPODEEMIC SYKINGE. 

— viz., the P. T. 0. — and concluding with the 
most potent the Old Tuberculin. In very sen- 
sitive cases, however, the use of the bacillary 
emulsion may, owing to its very slow absorp- 
tion, possess distinct advantages. When, on 
the contrary, toxemic symptoms are in abey- 
ance, it would appear to be more reasonable, 
perhaps after a preliminary course with a tox- 
in preparation such as Old Tuberculin, to en- 
deavor to establish a true anti-bacterial im- 
munity with the aid of T. R. and bacillary 
emulsion. Whatever preparation is utilized, I 
feel sure that the autogenous preparation is ne- 
cessarily the most suited to the case, and the 
ease with which the tubercle bacillus can now 
be isolated from the sputum will facilitate 
greatly the experimental confirmation of this 
view. In default of the autogenous tuberculin, 
a polyvalent stock preparation is next to be 
recommended, while the combination of human 
and bovine strains, which I first advocated 
three years ago, appears to possess distinct ad- 
vantages. 

The Control of Dosage and Interval. — (1) 
According to Wright's method; (2) according 
to Koch's method, modified according to more 
recent experiences. 

1. In Wright's methods, as we have already 
seen, the object is to give a series of indepen- 
dent immunizing stimuli, whereby the general 
well-being is improved without any regard be- 
ing paid to increase of tolerance or diminu- 
tion of sensitiveness. If the method be con- 



THE HYPODERMIC SYRINGE. 275 

ducted in its entirety, the control of dosage 
and interval is by means of determinations of 
the opsonic index, the aim being to employ 
such doses as will induce the maximum use 
of index and will maintain it at a high 
level for the longest possible time, reinocu- 
lation being performed as soon as the de- 
cline of index sets in, and increment of dosage 
being made when the old dose no longer proves 
efficient in these directions. The initial dose 
of any tuberculin preparation usually employ- 
ed in this method varies from 0.000001 c.c. to 
0.00001 c.c, and only exceptionally is it finally 
raised above 0.00001 c.c. to 0.0005 c.c. The in- 
terval between the administrations varies from 
ten to fourteen days. 

Occasionally the method is employed more 
empirically, the guidance of temperature chart, 
general condition, and past clinical experience, 
being substituted for that of index. As we 
have already seen, this system of small infre- 
quent dosage is admirably adapted for the 
treatment of localized and surgical tubercu- 
losis, but the general consensus of opinion now 
is that it is ill-adapted for the treatment of pul- 
monary tuberculosis and is accordingly being 
more and more discarded in favor of Koch's 
original method suitably modified. 

2. The Method of Immunization According 
to Koch, Also Known as the Intensive Method. 
— In this method the aim is to train the tissues 
to be able to cope with such doses of tuberculo- 
toxin as are liberated from the infected foci 



276 THE HYPODERMIC SYRINGE. 

without evincing signs of pronounced constitu- 
tional disturbances. In order to achieve this end 
tuberculin is administered at short intervals in 
rapidly increasing doses, for this has been 
found to be the only way in which hypersensi- 
tiveness can be overcome and tolerance in- 
duced. The cure of the focal lesion is left to 
natural processes, these being merely stimu- 
lated to increased action by the hyperemic con- 
dition there induced by the inoculations. 

Some authorities there are who endeavor to 
achieve the desired end by so adjusting their 
stimuli that constitutional disturbances are 
avoided completely is possible; others adjust 
their stimuli so as to produce such disturbances 
and regard them as evidences of efficient dos- 
age ; others, again, adjust their stimuli without 
any regard to the production or not of consti- 
tutional disturbances, aiming chiefly at being 
able to administer the highest possible dose of 
tuberculin in the shortest possible time. It is 
quite outside the scope of this work to go into 
these various methods; the one most in favor 
is that whereby the dosage is made the highest 
possible that will just avoid the production of 
marked constitutional disturbances. Whatever 
the preparation of tuberculin employed — and 
some prefer to employ Old Tuberculin through- 
out, others T. R., or B. E., or Beraneck's tuber- 
culin throughout, while others, again, prefer to 
employ P. T. 0. P. T., and Old Tuberculin in 
sequence — the initial dose is quite small. Thus, 
Denys and Wolff-Eisner begin with not more 



iHE HYPODERMIC SYBINQS. 277 

than 0.000001 c.c, Aufrecht with 0.000025 c.c, 
Bandelier and Eopke with 0.000001 to 0.00001 
c.c, Neumann with 0.000005 c.c, Krause with 
0.00002 c.c, Moller with 0.000001 c.c, Bande- 
lier and Ropke with 0.00002 to 0.0002 c.c, and 
Romisch with 0.0002 c.c of T. R. or B. E. In 
three or four days the second dose is given, dif- 
ferent authorities making different increments 
on the initial dose ; thus making use of a double 
dose, but Bandelier and Ropke use one increas- 
ed by half and Neumann makes an increment 
of one-third only. Thereafter different scales 
are employed; some use the progression, 1, 2, 
3, 4, 5, 6, 7, 8, 9, 10, 20, 30 and so on wherein 
there is a sudden marked increase after each 
series of ten inoculations; others use a pro- 
gression such as 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 15, 20 
and so on; while Bandelier and Ropke advise 
1, 1.5, 2, 3, 5, 7, 10, 15, 20, etc Whatever the 
notation employed for estimating the appropri- 
ate series of dosage, nearly all authorities who 
follow the system of avoiding reactions adopt 
the following principle when a reaction is pro- 
duced; they wait till all signs of the reaction 
have passed off, which varies from three to 
seven days, and then begin again, either with 
the dose which last failed to produce a reac- 
tion or with one of half this amount and then 
increase as before. 

As regards to final dosage which in the ab- 
sence of a reaction thereto is regarded as dem- 
onstrating that a condition of full tolerance 
has been attained, authorities slightly differ; 



278 THE HYPODEEMIC SYBXNGE. 

1 c.c. of the undiluted tuberculin is the limit 
fixed by most, but 0.1 c.c. is regarded as suffi- 
cient by many. These latter, of whom Pe- 
truschky is one of the chief advocates, alter- 
nate periods of treatment for three months. 
After the maximum has been attained, the 
treatment is discontinued for three months and 
then begun again ab initio, three or four such 
courses being administered whenever possible. 
All these authorities unite in disregarding 
reactions at the foci of disease and state that 
the dosage which will produce a general reac- 
tion is less than the dosage which will produce 
a focal reaction of such magnitude that it can 
be observed. In this I unhesitatingly state 
that they are in entire error. If sufficient care 
is taken to observe and record with accuracy 
the clinical signs in the chest before the ad- 
ministration of such a dose of tuberculin as 
will produce none but the slightest possible 
signs of general reaction, and these observa- 
tions are continued at frequent intervals, such 
as six, twelve, twenty-four and forty-eight 
hours, after the inoculations, I am certain that 
in all but a very small percentage of cases 
marked changes in the physical signs can be 
detected, changes precisely similar in charac- 
ter, if less in degree, than those already de- 
scribed on pp. 399-406 (where the author gives 
consideration to the use of other vaccines^ in 
the treatment of mixed infections), as being 
produced in response to an inoculation with 
an efficient dosage of a vaccine of catarrhal or- 



THE HYPODERMIC SYRINGE. 279 

ganisms, or of one corresponding to the organ- 
isms constituting the mixed infection. I would 
maintain that herein lies by far the best, easi- 
est and most reliable guidance to the appropri- 
ate dosage and intervals. Raised tolerance and 
diminished sensitiveness to tuberculo-toxin are 
desirable objectives, but they are not the real 
objective that we should have in mind. This 
is, firstly, the improvement of the general con- 
dition; secondly, the improvement of the focal 
condition; thirdly, the extinction of the infec- 
tion, and that scheme of dosage is obviously 
the best which produces the greatest ameliora- 
tion in the focal condition, all other things be- 
ing equal. Surely it is only logical then, to 
claim that the best basis upon which to found 
a scheme of dosage is that built upon the 
changes produced at the foci of disease. It is 
on such lines that I now treat all my phthisical 
patients and the principle I have adopted is as 
follows : Begin with a very minute dose of that 
tuberculin which seems best adapted to the 
case. By a very minute dose I mean 0.00001 
e.c. for apyrexial cases, and 0.000002 to 
0.000005 c.c. for pyrexial cases. The effect of 
this inoculation is closely watched and re- 
corded. If no reaction or improvement occurs 
within three days, the initial dose is repeated; 
if, again, no reaction or change within three 
days, double the initial dose is given and so on. 
Once a dose produces a focal reaction — and I 
have never yet seen a dosage which produced 
a general reaction fail to produce a focal one 



280 THE fiYfODEBMtC SYRINGE. 

also — close observation is kept upon the al- 
tered physical signs. It may be stated as an 
axiom that in a case capable of making im- 
provement, any dosage which will within 
twenty-four hours produce a reaction at the 
foci of disease, as evidenced by apparent in- 
crease of the involved area, increased moisture 
of the sounds or multiplication of their num- 
ber, will also, after a variable period — it may 
be one, two, three or more days — likewise in- 
duce a more than corresponding amelioration 
in the physical signs, so that there will be a 
time when the focal condition is better than it 
was before the inoculation was performed. Af- 
ter a further period — it may be of one, two 
three or more days — retrogression will begin 
and this is the signal for an immediate reinocu- 
lation. Under this system, which I would 
maintain is the most logical and scientific one 
yet devised, if unfortunately the one calling 
for the most care and attention on the part of 
the doctor, increase of dosage is indicated only 
by failure of production of an immunizing re- 
sponse at the focus of disease, and may be 
made according to the progression 1, 1.5, 2, 3, 
5, 7, 10. Occasionally a focal reaction of the 
following type is produced. Instead of in- 
crease in the area of apparent involvement and 
of the moisture of the sounds, there is a dimin- 
ution in these directions within twelve to twen- 
ty-four hours, either with or without the pro- 
duction of a slight general reaction. This is 
to be regarded as indication of a minimal effi- 



THE HYPODERMIC SYEINGE. 28l 

cient dosage, and of the advisability of an in- 
crease being made therein at the next admin- 
istration. 

Only very rarely, indeed, have I found a dos- 
age produce a general reaction, and at the 
same time fail to produce a focal one. On one 
occasion a change to B. E. from Old Tuberculin 
overcame the difficulty; on another occasion I 
could find no scheme of dosage that would suit 
the patient. I found it impossible to increase 
the dose of Old Tuberculin beyond 0.00002 c.c. 
without giving rise to marked general reaction 
and considerable constitutional upset, and de- 
cided that it would be wise to discontinue tub- 
erculin treatment for a time and then recom- 
mence with 0.000001 c.c. B. E. 

The one thing above all which should always 
be borne in mind is that whenever the system 
to which one may incline, whatever the scheme 
marked out for the treatment of any case, the 
man remains the prime consideration and not 
the scheme, and that when events are not tak- 
ing the desired course, the one thing to do is 
to reconsider the case minutely and endeavor 
to learn in what essential particulars modifica- 
tions may be required. 

Autoinoculation in Phthisis. — To Marcus 
Paterson is entirely due the credit of demon- 
strating the great value of the autoinoculation 
method of treatment in pulmonary tuberculosis 
and to those who are interested in the method 
and would learn how to apply it and what it 



282 THE HYPODERMIC SYRINGE. 

can achieve, I would advise the perusal of this 
comprehensive monograph on the subject. 

The facts bearing on the method are as 
follows : 

1. That the irregular pyreias of pulmonary 
tuberculosis are due to excessive and ill-or- 
dered autoinoculations with tuberculo-toxin 
derived from the infected foci. 

2. That these can often only be controlled 
by the most absolute or so-called " typhoid' ' 
rest. 

3. That the reparative processes and the ac- 
quirement of a high degree of tolerance to 
tuberculo-toxin may be greatly assisted by the 
induction of carefully ordered autoinoculation 
by means of graduated exercise and labor these 
autoinoculations being induced after adequate 
control of their spontaneous production has 
been gained if necessary, by the application of 
absolute rest. 

That the method is one of extreme value may 
be at once admitted, but it has its disadvan- 
tages, among which are mentioned : 

1. It can only be carried out thoroughly in 
institutions where the patients are well under 
control and where facilities exist for the pro- 
vision of labor of various kinds and various 
grades. 

2. That, strictly, it is only applicable to 
cases from which mixed infection is absent, for 
just as autoinoculation is induced with tuber- 
culo-toxin, so autoinoculation is induced with 
the products of mixed infection and no means 



THE HYPODERMIC SYRINGE. 283 

are available of ascertaining how much of the 
autoinoculatory effects, which are measured 
by means of the temperature and pulse charts, 
are due to the tuberculo-toxin and how much 
to the latter toxins. 

3. That whereas at the beginning of treat- 
ment, when the induction of only small autoin- 
oculations is required, a practically unlimited 
amount of autoinoculation can be induced, as 
the case proceeds to "arrest" of the infective 
process and the tissues require large stimuli to 
produce immunizing effects, small stimuli only 
are capable of production. Paterson 's conten- 
tion is that if signs of autointoxication cannot 
be induced by a day's hard manual labor, there 
can be little danger in allowing such a patient 
to return to his occupation. This would be 
true were it the case that extinction of the in- 
fection and impossibility of producing autoin- 
oculation effects were synonymous; this, un- 
fortunately, is not the case, and the return of 
such an individual to hard work in unfavor- 
able surroundings is extremely apt to lead to 
speedy relapse. It is somewhat unfortunate 
that Paterson should be prepared to regard the 
disease as arrested in an individual who con- 
tinues to expectorate tubercle bacilli. 

Personally, I think that there is a great field 
for the application of the valuable lessons 
which Paterson has learned and teaches. There 
is no tuberculin so well adapted to the treat- 
ment of a case as that formed by the affected 



284 THE HYPODEEMIC SYEINGfi. 

individual for himself, but I think the wisest 
procedure would be as follows: 

1. Control autoinoeulations by rest, abso- 
lute if required. 

2. Eliminate mixed infections by means of 
autogenous vaccines. 

3. Raise tolerance by a short course of Old 
Tuberculin. 

4. Proceed to autoinoculate by means of 
graduated exercise and work. 

5. When these stimuli fail to produce any 
reaction, recommence tuberculin treatment, 
perhaps best with the bacillary emulsion; em- 
ploy the intensive method, and proceed to mas- 
sive doses, and so endeavor to raise antibacte- 
rial as well as antitoxic immunity and elimin- 
ate the bacterial infection. 

This elaborate method might well prove to 
be the best yet devised for the treatment of pul- 
monary tuberculosis. 

Citron in his " Immunity.' ' 1912, p. 61, give* 
the following suggestions as to the technical 
details of treatment of tuberculosis by inocu- 
lations : 

1. The inoculation should, if possible, be 
given in the morning hours, for a restless night 
usually follows an injection in the evening. 

2. It is best to so arrange the dilutions that 
the patient receives a fraction of 1 c.cm. at 
each injection. 

3. The site of injections should be alternat- 
ed between the back and breast. 



THE HYPODERMIC SYRINGE. 285 

4. The temperature should be taken every 
two or three hours and a chart of the same 
kept. 

5. Disturbances in the general condition of 
the patient without the presence of fever are 
to be considered in the light of general reac- 
tions just as fever without other disturbances. 

6. The patient's weight should be taken 
regularly every week and then the dose should 
be increased provided no loss in weight has 
taken place. 

7. In cases where the pulse increases in rate 
or becomes poorer in quality, the treatment 
should be undertaken very carefully and the 
pulse constantly kept as a guide. Slowness of 
pulse can, as a rule, be considered a signum 
bonum. 

Other Serums and Bacterins. — In the forego- 
ing pages have been mentioned only those 
agents more commonly in use at this time; 
those of proven value. It is very probable, in 
light of the rapid strides being made in these 
lines, that this work will become antiquated 
and that very shortly, through the discovery 
and application of other products of this sort. 
It is likewise probable that many of the serums 
and vaccines, now being employed, will be put 
to greater use in time to come. While this lit- 
tle book is supposed to deal only with the hy- 
podermic syringe, we have purposely given 
more than a little space to the consideration of 
biologic preparations, believing, in so doing, 
that we add to the value of the work thereby. 



CHAPTER XV. 

Anesthesia. 

General Anesthesia. — That the hypodermic 
syringe is a useful adjunct in connection with 
general anesthesia has been evidenced time and 
again. In many cases of emergency, following 
accident, we find a marked shock, and through 
being able to apply either supporting agents in 
such a way as to be assured of prompt and effi- 
cient action, many lives have undoubtedly been 
saved. In those accidents, wherein many are 
injured, the hypodermic syringe plays an im- 
portant role. With the introduction of hyos- 
cine and morphine, or scopolamine and mor- 
phine, it became possible for the surgeon to 
place those whom he could not give immediate 
attention at rest, and it has been found that, 
after the injection of either of these combina- 
tions the patients were in better condition to 
receive the volatile anesthetic agent. If there 
was collapse, with or without internal hemor- 
rhage, either of these combinations or atropine 
in full dosage, hypodermically, brought about 
a marked change for the better in the patient. 
The pulse which had been small, rapid and 
light previously, showed improvement and th^ 



288 THE HYPODERMIC SYEINGE. 

surfaces became more nearly normal, with the 
disappearance of the cold, clammy skin. 
Strychnine, likewise hypodermically, acted to 
increase the general tone and to restore the 
conditions to the normal. If there was a large 
loss of blood, infusion, either subcutaneously 
or intravenously, of normal salt solution, have 
been available through the hypodermic method. 
For a number of years, some five or six 
decades, it has been the habit to induce general 
anesthesia through the use of chloroform, 
ether, ethyl chloride and ethyl bromide, as vol- 
atile agents and nitrous oxide. Recently, with- 
in the past decade, with the recognition of the 
deep slumber produced by either hyoscine or 
scopolamine, in combination with morphine, it 
was proposed that the volatile drugs be omitted 
and that the obtunding effect be produced with 
the hypodermic use of either of these combina* 
tions. There are numerous reports of cases nt 
which these combinations worked well but it 
was found that it was not possible to invari- 
ably keep the patient fully anesthetized with 
their use. Furthermore, in certain procedures, 
where absolute muscular relaxation was de- 
sirable, this latter condition did not invariably 
occur. This was particularly true in operations 
involving the abdomen. With the recognition 
of this fact, further attempts to employ either 
of these combinations, to the exclusion of the 
volatile anesthetics, were discontinued. How- 
ever, despite the fact that hyoscine and mor- 
phine or scopolamine and morphine were not 



THE HYPODERMIC SYRINGE. 289 

absolutely satisfactory alone, it was found that 
the use of either, prior to the administration 
of either chloroform or ether, better prepared 
the patient for the volatile drug and that he 
went to the scene of operation in a peaceful 
state of mind which very largely overcame the 
usual tendency to either operative or post-oper- 
ative shock. In fact, those who were thus pre- 
pared, showed but little difference in general 
condition either prior or subsequent to opera 
tion. This fact being recognized, it has become 
the routine habit for a very large number of 
surgeons and anesthetists to employ these ob- 
tunding drugs, hypodermically, prior to exhibi 
tion of the volatile anesthetics. 

The technic employed is extremely simple. 
Having prepared the patient for operation in 
the general way (excepting in emergencies, 
where prior preparation is usually impossible), 
two hours prior to the time of going onto the 
table, a subcutaneous injection of hyoscine or 
scopolamine 1/100 grain and morphine % grain 
is administered. If the patient is not quiet, or 
sleeping at the end of an hour, a second half 
dose is administered. As a rule the single dose 
is sufficient to both quiet the patient and allay 
his fears, both of the operation and the volatile 
anesthetic. In emergencies, where shock has 
followed accidental injury, either of these com- 
binations will place the patient at rest, and 
that quickly in the general run of cases. Not 
only do these combinations act in the manner 
above mentioned, but they seem to overcome 



290 THE HYPODEEMIC SYEINGE. 

many of the unpleasant features usually asso- 
ciated with the use of the volatile drugs, espe- 
cially chloroform and ether. Not as much of 
either of the latter is required as when they 
are administered without such prior prepara- 
tion. The first stage of anesthesia is decreased 
to a marked extent, and the stage of excite- 
ment is practically or wholly overcome and in 
many extensive operations the patient has been 
held under the volatile agent over a consider- 
able time with less of the anesthetic than had 
previously been required to bring him under 
its influence initially. This lessening of either 
chloroform or ether practically does away with 
the general drug effects which at times follow 
in the wake of these agents, as the patient is 
not overdosed. The nausea and vomiting, sub- 
sequent to anesthesia, are as a rule, reduced or 
wholly obliterated. Not only do these obtund- 
ing drugs place the patient in better condition 
to receive the volatile agents, but subsequent 
to operation he is, almost invariably, assured of 
several hours of peaceful sleep, from which he 
awakes refreshed and better able to contend 
with the conditions usually following operative 
procedure. Not only does he awake within his 
own room and bed, and away from the usual 
horrors of the operating theater, but as a rule 
his knowledge of post-operative procedures is 
absolutely nil. Prior to his awakening, proc- 
toclysis, if indicated, has been done and he 
does not have to undergo this during his wak- 
ing hours. In fact, when he comes from under 



THE HYPODEKMIC SYEINGE. 291 

the anesthetic, it is with an assurance that he 
will pass the coming hours as nearly comfort- 
able as is possible, all things considered. Hy- 
podermoclysis is also practiced prior to the 
awakening of the patient and without pain or 
discomfort to him, it usually being concluded 
before he awakens. 

In obstetrical work the hyoscine and mor- 
phine, or scopolamine and morphine, combina- 
tions are employed with good effect and it not 
infrequently happens that other obtunding or 
anesthetic agent becomes unnecessary. With 
the appearance of the pains, a half dose is ad- 
ministered hypodermically. This does not 
have any seeming effect upon the uterine con- 
tractions but does have a marked effect upor 
the associated pains in some instances wholly 
obliterating them. The patient usually sleeps 
between pains but with the coming contrac- 
tions awakens and assists the obstetrician in 
the usual manner. In some instances it may be 
necessary to give either a full dose initially or 
a second half dose or to administer a few whiffs 
of chloroform. Although the woman may com- 
plain more or less pain at the time, she rarely 
has any subsequent memory thereof and in 
many cases it has been reported that the pa- 
tient has awakened, asking "when will the 
baby be born," or "is it all over," or other 
query denoting the fact that she had no realiza- 
tion of pain. In event of lacerations, these 
may be repaired during the subsequent stage of 



292 THE HYPODERMIC SYBINGE. 

slumber and frequently without the use of a 
single drop of a volatile anesthetic. 

In connection with general anesthesia, and 
to overcome operative or post-operative shock, 
Crile has given the hypodermic added value. 
To overcome shock arising from operation, he 
produces local anesthesia of the skin, as well as 
of the deeper tissues, through the injection of 
cocaine, novocaine, eucaine, stovaine or urea 
and quinine, thus blocking off the fields of op- 
eration, in so far as sensibility is concerned. 
Not only does this obtund the site of operation 
during the time of operation, but if urea and 
quinine are employed the anesthesia, locally, 
continues for some time after, thus giving the 
patient freedom from the usual post-operative 
pains in and about the wound. In patients so 
treated he reports that the tendency to shock 
has been practically wiped out. In amputa 
tions, the injection of novocaine into the larger 
nerve trunks, prior to severing, likewise re- 
duces the tendency to shock. 

Spinal anesthesia with injections of stovaine, 
tropacocaine and other obtunding drugs of the 
like nature, may be practiced prior to the use 
of the volatile anesthetics, thus reducing the 
amount of the latter employed. The technic of 
spinal anesthesia will be considered on another 
page. 

With the use of either hyoscine and mor- 
phine or scopolamine and morphine for their 
general obtunding effect and one of the local 
anesthetics mentioned, at the site of operation, 



THE HYPODERMIC SYRINGE. 293 

the danger of shock is practically obliterated 
and the comfort of the patient is very greatly 
increased. The use of both should be routine 
practice. 

Local Anesthesia. — It is probable that Sar- 
gent and Russell in their "Emergencies of Gen- 
eral Practice/ ' 2nd Edition, page 4, give as 
good a description of the technic of local anes- 
thesia as is obtainable and the following is 
quoted from that authority: 

Some operations of urgency are best done 
under local anesthesia, as for example, a stran- 
gulated hernia in a patient who, on account of 
age, shock, or some cardiac, pulmonary or 
other disease, is an unsuitable subject for a 
general anesthetic. Some abdominal opera- 
tions, such as the relief of intestinal obstruc- 
tion, may, under similar circumstances, be per- 
formed under local anesthesia. It is of special 
value in operating for empyema when the pa- 
tient is very ill and the respiration greatly 
embarassed. 

Speaking of the local obtunding of external 
and other tissues, they speak as follows: 

(a) The Application of Cold. — This method 
is almost restricted to the incision of subcutan- 
eous abscesses. A fine spray of ether or ethyl 
chloride is directed upon the site of the pro- 
posed incision until the skin is literally frozen, 
when the cut can be made without any pain 
being felt. The objections to this method are 
the hardness of the tissue which has to be cut 



294 THE HYPODEBMIC SYRINGE. 

through and the pain which is experienced as 
the cold passes off. 

(b) Local Application of Analgesic Drugs. 
— The uncertainty and risks, attending the use 
of cocaine renders its employment undesirable 
particularly in the quantities in which it would 
be required for an operation of any magnitude. 
There are, however, other drugs, which while 
possessing sufficient analgesic properties, are 
almost if not quite free from toxity even in 
comparatively large doses. They can, more 
over, unlike cocaine, be sterilized by boiling. 
These drugs are eucaine, stovaine, novocaine 
and tropacocaine. It is found that if epine- 
phrin is used together with the analgesic drug, 
the effect is increased both in intensity and 
duration. A large number of different for- 
mulae have been recommended by various writ 
ers, and many preparations can be obtained 
commercially in sealed vials, sterilized and 
ready for use. One of the best is Professor 
Braun's solution, consisting of novocaine, 0.5 
per cent, suprarenin borate, 0.00064 per cent, 
and sodium chloride, 0.9 per cent. 

For an operation of any magnitude a dose 
of morphia of about % grain should be given 
before the operation is begun. The patient 
should be prevented from seeing what is going 
on and his attention may be distracted by con- 
versation during the operation. 

These drugs may be employed in different 
ways, namely by (1) general infiltration of the 
field of operation, and (2) deliberate " block- 



THE HYPODERMIC SYRINGE. 295 

ing" of the main sensory nerves by injection 
into or around them, not necessarily at the site 
of operation but also at a distance; for ex- 
ample, blocking the ulnar nerve at the wrist 
for an amputation of the little finger. 

The anesthesia appears much more rapidly 
if the injection is made into the nerve trunk 
than when perineural infiltration is employed. 
C. M. Page is of the opinion that stronger solu- 
tions of the drugs do not act much more rapid- 
ly than dilute, though their effect is more per- 
sistent; that in fact the bulk of the solution is 
of more importance than its concentration. 
The application of a Martin's bandage above 
the site of operation in the case of the limbs, 
has the effect of prolonging the anesthesia by 
retarding the diffusion and absorption of the 
drug. 

(1) General Infiltration. — A large hypoder- 
mic syringe provided with a specially long 
sharp needle should be used, though the ordi 
nary pattern can quite well be made to serve 
in an emergency. The needle is thrust into the 
skin so as to lie in the deeper layers of the 
true skin and not in the subcutaneous tissue, 
along the line of the proposed incision, and 
the injection made during the withdrawal. 
This insures, if properly carried out, absence 
of pain during the division of the skin. As the 
deeper parts are reached they can be rendered 
insensitive by repeated applications of the so- 
lution, or by injection into the nerves. The 
actual time of the operation is thus unavoid- 



296 THE HYPODERMIC SYRINGE. 

ably lengthened, but this is a matter of little 
moment compared with the advantages which, 
in selected cases, the avoidance of a general an- 
esthetic confers. 

(2) Intra- and Peri-Neural Injection. — 
These methods envolve a more accurate knowl- 
edge of topographical anatomy than the fore- 
going and in emergency work would apply 
chiefly to amputation. The principle has been 
applied to the operation of rib resection for 
empyema by C. M. Page (St. Thomas' Hos. Gaz. 
Dec. 1909), whose method is best described in 
his own words: 

"Before the operation area is washed, a 
puncture is made on the verterbral side of the 
proposed incision, if possible to the outer side 
of the erector spinae. The needle is passed in 
at the level of the intercostal space above the 
rib to be resected, the point is first made to 
impinge on the surface of the upper rib of the 
space and is then made to pass downwards till 
it dips into the subcostal groove; 3-5 c.c. of the 
selected solution are here injected. Two fur- 
ther punctures are made in relation to the two 
ribs below this, and the same procedure re- 
peated, i. e., including the rib to be resected. 
This effects a perineural infiltration of the in- 
tercostal nerves. Just before commencing the 
operation the skin itself in the line of incision 
is infiltrated. If about ten minutes have 
elapsed from the time of the first puncture, 
complete anesthesia of all the structures in- 
volved in subsequent manipulation will be pres- 



THE HYPODERMIC SYRINGE. 29? 

ent, the entire insensitiveness of the perioste- 
um, bone and pleura, being in marked contrast 
to the pain present in those cases where sim- 
ple infiltration alone has been employed/ ' 

Quinine and urea hydrochloride, which salt 
has come into prominence of late in the United 
States, for the purpose of obtaining local anes- 
thesia by infiltration, is not mentioned by Sar- 
gent and Russell. It has all of the advantages 
of the drugs above mentioned and in addition 
is practically harmless in so far as untoward 
systemic effects are concerned. It is employed 
in much the same manner as are the other local 
anesthetics. Merck gives the dose as from 1% 
to 8 grains in 50 per cent, aqueous solution. 
Recently much lower percentage solutions have 
been used ; 1, 2, 3 and 4 per cent, solutions 
have been found as effective as the higher 
one suggested, and less liable to act as ir- 
ritants, with possible abscess formation. Crile 
recommends this agent for the "blocking 
off" of the site of operation. The effects of 
this salt pass over a longer period than do 
those of any of the other drugs employed for 
the obtaining of local anesthesia and this one 
thing recommends it, especially in the obvia- 
tion of post-operative pain and discomfort. 

Again referring to Sargent and Russell is 
found the very complete description of spinal 
anesthesia and the technic of application 
thereof : 

We are not concerned in this chapter with 
the merits or demerits of spinal anesthesia as 



298 THE HYPODEEMIC SYRINGE. 

a rival of general anesthesia in routine work. 
But as a means of preventing shock in grave 
emergency operations this method undoubtedly 
has a place. When anesthesia is satisfactorily 
induced, the afferent impulses from the opera- 
tive field are effectually prevented from reach- 
ing the sensorium; with general narcosis this 
effect is not produced unless the depth of anes- 
thesia is far deeper than is necessary to abol- 
ish consciousness. 

Against this very great advantage must be 
set the fact that the psychical factor of shock 
is not abolished as it is with general narcosis 
and this objection is increasingly greater in 
proportion to the patient's racial or individual 
sensitiveness. Crile has advocated the com- 
bined use of spinal and general anesthesia in 
certain cases. The former prevents shock-pro- 
ducing afferent impulses from reaching the 
central nervous system, whilst the latter, given 
in the small quantity necessary to abolish ac- 
tual consciousness, does away with the shock- 
producing psychical factor. The hypodermic 
injection of morphia and scopolamine in addi- 
tion to the spinal anesthesia has a similar ef- 
fect. Our own experience of spinal anesthesia 
has not been encouraging, but from a small 
number of cases we are not entitled to speak 
dogmatically. Our conclusions are drawn in 
the main from two sources — a paper by C. M. 
Page dealing with a large number of reported 
cases as well as his own experience and papers 



THE HYPODERMIC SYRINGE. 299 

by H. Tyrrell Gray based upon his large per- 
sonal experience of the method in children. 

Page, in December, 1909, tabulated over 23,- 
000 cases collected from various sources as 
follows : 

Fatal Oculo- Rate ofMortality 

No. of Col- motor 

Drug Cases A B lapses Palsies A Total 

Cocaine 6,875 12 12 54 .. 1 in 573 1 in 271 

Tropacocaine 7,459 6 5 12 3 1 in 1243 1 in 675 

Stovaine ... 6,234 7 1 16 24 1 in 890 1 in 670 

Eucaine 817 1 1 in 817 1 in 817 

Novocaine .. 1,35^ 3 .. 10 7 1 in 449 1 in 449 

Alypin 414 3 1 5 .. 1 in 138 1 in 103 



Totals 23,154 32 20 97 34 1 in 722 1 in 444 

A — Deaths attributed to the direct action of the drug. 
B — Deaths occurring- when some other condition 
sufficient of itself to produce death, was present. 

Of these drugs stovaine, novocaine and 
tropacocaine are most frequently employed. 
The last named appears to be at once the safest 
and least efficient. Stovaine has the great dis- 
advantage of being precipitated and rendered 
inert by certain chemicals, particularly alka- 
line fluids. If, then the instruments are boiled 
as is usually done, in water with soda added, 
the drug is precipitated. It is necessary to use 
plain water for sterilizing the syringe and 
everything that is used for the spinal opera- 
tion. 

Many different formulae are employed. H. P. 
Dean recommends: Stovaine, 0.1 grm; sodium 
chloride, 0.1 grm.; and distilled water, 1 grm. 
A. E. Baker uses 10 per cent, stovaine with 
glucose 5 per cent, and distilled water 85 per 
cent. 



300 THE HYPODERMIC SYRINGE. 

The following solution can be obtained com- 
mercially ready for use, in sealed phials, each 
containing three cubic centimetres: 

Novocaine 0.15 grm. (5 per cent) 

Suprarenin 0.000325 grm. 

The dose of this fluid should be from 2 to 3 
cubic centimetres, or 35 to 50 minims. 

H. Tyrrell Gray (Lancet, June 11th, 1910) 
reported 300 personal cases in children, with 
one death and six failures to produce anes- 
thesia. He has shown conclusively that the 
method can be employed satisfactorily in chil- 
dren, the psychical element in the production 
of shock being almost or entirely absent. Many 
of the operations in this series were performed 
for conditions of extreme gravity and it ap- 
pears certain that the abolition of shock and 
the absence of the toxic effects of a general 
anesthetic contributed in great measure to the 
brilliant results obtained in some of these cases, 
notably the recovery of a child only seven 
months of age after resection of an intususcep- 
tion and anastomosis by H. A. T. Fairbank. In 
this connection one point of special interest is 
brought out by Gray, namely, that "so long as 
the anesthesia is complete, surgical shock is 
altogether absent, but that when the effect of 
stovaine on the nerve roots begins to wear off 
and anesthesia passes into analgesia, signs of 
shock begin to appear.' ' It must not be sup- 
posed that spinal anesthesia is devoid of dan- 
ger, though doubtless with increasing familiar- 



THE HYPODERMIC SYRINGE 301 

ity with its technique and improvements in the 
preparation of the drugs employed, these dan- 
gers will be obviated or minimized. Death has 
occurred from respiratory failure and bulbar 
paralysis from the drug reaching too high a 
level and from meningitis. Serious and alarm- 
ing after-effects have been recorded many 
times, such as persistent vomiting, severe head- 
ache, rigors, collapse, respiratory difficulty and 
paralysis of the bladder followed by cystitis. 

Technique. — An ordinary antitoxin syringe, 
provided with a specially long, sharp needle, 
may be used for the injection. If the patient 
is well enough, the sitting posture is the most 
convenient; if not, he should be lying upon one 
side with the back flexed as much as possible. 
The needle may be entered in the mid-line just 
above the spine of the fourth lumbar vertebra, 
which lies on a level with the highest point of 
the iliac crests and thrust forwards and a lit- 
tle upwards ; or it may be entered half an inch 
to one side of the mid-line and thrust forward, 
inward and upward, so as to pass between the 
laminae of the third and fourth lumbar verte- 
brae. As soon as the needle has entered the 
spinal theca, cerebro-spinal fluid will flow from 
it. It is essential that a flow of cerebro-spinal 
fluid should occur before the injection is made, 
in order to be quite certain that the point of 
the needle is in the subdural space. The syr- 
inge should now be connected with the needle, 
some of the cerebro-spinal fluid allowed to mix 
with the solution in it and the injection per- 



302 THE HYPODERMIC SYRINGE 

formed. The patient should immediately be 
placed in the recumbent position, with the 
shoulders somewhat raised so as to prevent 
the drug reaching a dangerously high level. As 
the drug takes effect there is first a feeling or 
numbness in the legs, followed by weakness 
and ultimately, after a few minutes, there will 
be complete analgesia and a varying degree of 
motor paralysis. 



CHAPTER XVI. 

Shock. 

Shock and collapse, until very recently, have 
been considered one and the same, in so far as 
the initial cause might be concerned but Crile 
has determined the fact that they are not due 
to one and the same cause, consequently the 
treatment is not relatively the same in both. 
He has shown that collapse is due to centri- 
petal influence from without upon the vaso- 
motor centers, sufficiently severe as to inhibit 
their activity temporarily but allowing of their 
restoration of function promptly under indi- 
cated treatment. Severe loss of blood may oc- 
casion collapse as may something appealing 
strongly to the moral senses. Shock is due to 
prolonged external stimulation, or repeated ac- 
tion of this sort and leaving a condition which 
does not respond immediately to the action of 
drugs and other agents employed for relief. In 
all cases of both collapse and shock, the nerve 
cells undergo change, according to Crile (Br. 
Med. Jour. Oct. 1, 1910). In the first mention- 
ed condition this change may be slight and the 
cells may recover promptly, while in shock 
there may be complete obliteration or disin- 



304 THE HYPODERMIC SYRINGE 

tegration of the nerve cells. In both conditions 
there is a lowering of the blood-pressure; in 
collapse the pressure may be restored easily as 
compared with shock, where restitution is 
based wholly upon the repair of the cells of 
the vaso-motor centers. Collapse then is really 
nothing more than a functional disorder and 
one in which the restoration of the normal is a 
matter of comparative ease, while shock be- 
comes an organic condition in which time is re- 
quired as well as remedial agents in the bring- 
ing about of the normal. 

Quoting from "Emergencies of General 
Practice, ' ' 2nd Edition, Sargent and Russell, is 
given a very clear idea of the clinical symp- 
toms of shock: 

The pulse is easily compressible, of small 
volume, rapid and sometimes irregular. The 
pressure may be estimated roughly by the feel- 
ing of the pulse but is more accurately deter- 
mined by some form of sphygmomanometer 
such as that of Riva Rocci. In old people the 
rigidity of the arteries may give a false im- 
pression of the blood-pressure and must be al- 
lowed for, lest the patient be assumed to be in 
better condition than he really is. Other im- 
portant symptoms are rapid, shallow and often 
irregular respiration, depressed mentation, gen- 
eral muscular weakness, lowered temperature, 
diminution or suppression of urine, sweating 
and an expression of a more or less character- 
istic kind, in which the face is pallid and 
pinched and the eyes sunken. 



THE HYPODERMIC SYRINGE 305 

In consideration of the prevention of shock 
the same authors offer the following : 

The precautions to be taken against shock as 
well as the measures to be adopted in its treat- 
ment, depend upon a clear conception of its 
causation, as well as its pathological anatomy. 

Crile has shown that the above-mentioned 
cell changes are caused by (a) severe and re- 
peated afferent impulses whether sensory in the 
ordinary meaning or not, e. g., from manipula- 
tion of intestines, or section of a large nerve 
trunk whilst the patient is under an anesthetic ; 
(b) psychical influences, particularly fear; (c) 
loss of blood ; (d) toxemia, either from bacte- 
rial toxins or drugs (ether and chloroform). 

In emergency work one or more of the above 
mentioned factors are likely to be already pres- 
ent when the practitioner first sees the patient ; 
the psychical influence and loss of blood in a 
severe injury; e. g., a cut throat; the alarm, 
pain, irritation of the peritoneum and toxic ab- 
sorption in a healthy patient suddenly seized 
with perforative appendicitis. In these cases 
not only has the shock already present to be 
treated, but all available measures must be 
taken to prevent additional shock during the 
operation. 

The psychical element can be minimized by 
allaying the patient's fears, by preventing him 
from seeing or hearing the preparations for 
operation, and also by the hypodermic injec- 
tion of morphia and scopolamine (hyoscinp 
hydrobromide) gr. 1-200 to 1-100. Loss of 



306 THE HYPODERMIC SYRINGE 

blood must be guarded against on ordinary- 
surgical lines. The effect of afferent impulses 
can be minimized by gentleness of manipula- 
tion and in the case of amputation by injecting 
novocaine into the large nerve trunks before 
dividing them. In suitable cases spinal anes- 
thesia may be used, in conjunction with min- 
imal dose of chloroform, as a means of prevent- 
ing shock in major operations upon the lower 
part of the body. 

In their attention to the treatment of shock, 
other than through proper anesthesia, these 
authors show the worth of hypodermic medica- 
tion very clearly as follows : 

Treatment of Shock. 

This consists essentially in adopting all the 
means available for raising the lowered blood- 
pressure. Naturally one first thinks of the 
rapidly diffusible stimulants, ether, alcohol and 
strychnine but too often their action is only 
analagous to whipping the tired horse; there 
may be a momentary response, only to be fol- 
lowed by a further fall and this is especially 
the case with alcohol and ether. The essential 
point is that the vaso-motor mechanism should 
be stimulated peripherally and not centrally; 
the blood-pressure must be raised and kept 
raised until the central vaso-motor mechanism 
has had time to recover. The means to this 
end are as follows: 

1. Drugs. — Adrenalin raises the blood-pres- 
sure by its action upon the peripheral ateri- 



THE HYPODERMIC SYEINGE 307 

oles. It may be given by hypodermic injection 
(5 minims of the 1 in 1,000 solution of adren- 
alin chloride) or better, by intravenous injection 
of saline solution containing 10 minims of the 
1 in 1,000 solution in 2 pints of fluid. In this 
form it is best given by the continuous or inter- 
mittent subcutaneous method, because by this 
means it is possible to continue the peripheral 
effect of the drug over longer periods, and in 
accordance with the requirements of the case 
as indicated by the blood-pressure. The effect 
of adrenalin is very transitory, its properties 
being rapidly lost in the tissues. It is, for this 
purpose, quite useless to give by the mouth. 
Hemisine is a commercial product containing 
the active principle of medulla of the supra- 
renal gland. Its action is that of adrenalin and 
it may be given by the mouth (5 to 15 minims 
of the 1 in 1,000 solution) or hypodermically 
(1 in 100,000). 

Tyramine is an active principle derived from 
ergot and may be given either hypodermically 
or by the mouth for the purpose of raising the 
blood-pressure in shock, its action in this re- 
spect being similar to that of adrenalin. It has 
the advantage that its effect lasts much longer 
than that of adrenalin. 

Preparations made from the posterior lobe 
of the pituitary gland have an effect similar to 
that of adrenalin and the effect lasts longer. 
These, when available, are used in preference 
to adrenalin when required for subcutaneous 
injection and the effect is stated to be better 



308 THE HYPODERMIC SYRINGE. 

when intramuscular injection is employed. One 
preparation is on the market as "vaporole 
pituitary extract' ' and is supplied in sealed 
glass phials, each containing 1 c.c. represent- 
ing 3 grains of fresh posterior lobe of the pitu- 
itary body. The dose is x /2 to 1 c.c. Another 
preparation which can be obtained in sealed 
phials ready for use is known as Pituitarian. 
Each phial contains 15 minims of fluid, equiva- 
lent to 3 grains of fresh posterior lobe of pitu- 
itary body, the amount suitable for a hypoder- 
mic or intramuscular injection. A third sim- 
ilar preparation is sold under the name of 
Pituitrin, of which 1 c.c. (17 minims) repre- 
sents 1.5 grains of the fresh posterior lobe. 

2. Saline Infusion. — By running normal sal- 
ine solution directly into the venous system or 
by its more gradual absorption from the rectum 
or subcutaneous tissues, the blood-pressure can 
be raised, but the effect is very transitory and 
the fluid is rapidly removed by the skin and 
kidneys. When given slowly and in combina- 
tion with adrenalin the effect can be prolonged 
considerably. 

The fluid to be used is sterilized normal 
saline solution, which can readily be made by 
dissolving a drachm of common salt in each 
pint of water. When, in case of emergency, 
common salt has to be used, the solution should 
be filtered through a piece of sterilized gauze 
or muslin in order to free it from hairs and 
other foreign matter. For rectal injection the 
fluid need not, of course, be sterilized, but for 



THE HYPODERMIC SYRINGE. 309 

the other methods sterilization must be carried 
out with the greatest care and throughout the 
operation the most scrupulous asepsis must be 
maintained. 

Intravenous Infusion. — This is by far the 
most rapid and efficient way of introducing 
fluid into the circulation and the one most gen- 
erally applicable. The apparatus required con- 
sists of a scalpel artery forceps, scissors, aneu- 
rysm needle, canula rubber tubing and funnel, 
thermometer, measuring glass, ligatures and 
sutures. 

Operation. — The skin over the front of the 
elbow having been thoroughly cleansed, the 
largest vein visible (usually the median basilic) 
is exposed by an incision an inch in length. It 
may be necessary to tie a bandage round the 
upper arm in order to render the veins suffi- 
ciently visible ; it need hardly be said that the 
bandage must be removed as soon as the canu- 
la is in place. By means of the aneurysm 
needle two silk ligatures are passed beneath 
the exposed vein, about an inch apart; the 
lower one is tied and the upper one left loose. 
The funnel, the tube and canula, all previously 
sterilized with scrupulous care, are then com- 
pletely filled with the saline solution at 105° 
F. (to which a little brandy, if thought neces- 
sary, may be added) so as to exclude all bub- 
bles of air. A small oblique incision is made 
into the vein and the canula introduced in an 
upward direction. The upper of the two liga- 
tures, which had been left loose is tied with a 



310 THE HYPODERMIC SYRINGE. 

single hitch so as to hold the canula in place. 
The fluid is now allowed to flow into the vein, 
the funnel being elevated as high as may be 
necessary to cause it to flow with moderate 
rapidity. This height is subject to great varia- 
tion, a free flow being sometimes obtained with 
an elevation of a couple of feet, whilst at other 
times the funnel must be raised three or four 
feet. When sufficient fluid has been introduced 
the canula is withdrawn, the ligature tied 
tightly and the wound closed. 

When the case is very urgent, the operation 
may be shortened by introducing a large anti- 
toxin needle directly into a vein, stabbing 
through the skin and vein wall in the direction 
of the heart and attaching the tube and funnel 
to the needle. 

In cases of severe hemorrhage it is often ad- 
visable to add to the normal saline solution a 
small quantity of adrenalin chloride, 10 minims 
of the 1 in 1,000 solution in 2 pints of saline. 
If more than 2 pints of fluid is necessary, the 
additional quantity should contain no adren- 
alin. The amount to be introduced is to be 
estimated by the effect upon the pulse. When 
saline alone is used, however much infused, the 
blood-pressure is only very temporarily raised 
above the normal. After an infusion sweating 
is sometimes most profuse and the amount of 
urine passed may be enormous. An undoubted 
danger attending the introduction of an exces- 
sive quantity of fluid directly into the circula- 



THE HYPODERMIC SYRINGE 311 

tion is oedema of the lungs, from which death 
occasionally occurs. 

Rectal infusion is likewise employed in the 
treatment of shock, but as this is without the 
bounds of the subjects considered within these 
pages, it will not be discussed. Sargent and 
Russell give this portion of the treatment 
thorough consideration. Again quoting from 
their work we obtain the following : 

Subcutaneous Infusion. — Saline solution can 
be absorbed with fair rapidity from the sub- 
cutaneous tissues and this is a method particu- 
larly adaptable for children. It is best given 
by the continuous method as follows : one or 
more large hypodermic needles are connected 
by means of a long piece of rubber tubing with 
a vessel containing the saline solution. Every- 
thing must be sterilized and the whole proced- 
ure conducted with the most scrupulous re- 
gard for asepsis. The needles are thrust into 
the subcutaneous tissue of the flank or chest 
wall and the vessel is suspended above the bed 
at such a height as to ensure the liquid being 
forced slowly into the subcutaneous tissue. It 
may be necessary to alter the position of the 
needle if a very tense swelling is produced. 
The temperature of the fluid must be kept con- 
stantly at 105° F. In this manner a pint or 
more can be introduced in the space of an hour 
but it is a tedious and sometimes painful meth- 
od and requires the undivided attention of a 
nurse. 



312 THE HYPODERMIC SYRINGE 

Intraperitoneal Infusion. — In abdominal op- 
erations saline solution may be left in the peri- 
toneal cavity from which it is rapidly absorbed 
into the circulation but the amount which can 
be introduced in this manner is not large and 
the method is obviously capable of but limited 
application. 



CHAPTER XVII. 

Syphilis. 

With the discovery of the cacodylates and 
later of arsenobenzol, the advantages of the hy- 
podermic treatment of syphilis was emphasized. 
A few adventurous practitioners had employed 
mercury hypodermically for some time but this 
method had not come into prominent use until 
after the introduction of the above-mentioned 
agents. Today, however, we see a marked 
change in the methods of treatment and not 
only are the arsenic but the mercurial com- 
pounds, as well, administered in this manner. 

During the earlier days of the hypodermic 
treatment of syphilis through the application 
of the mercurial salts it is very possible that 
some of the failures and disastrous results fol- 
lowing were due to the use of insoluble salts 
of this metal, as it is pointed out by Schamberg 
that numerous deaths have followed in the 
wake of the use of such agents. 

While it has been a recognized fact that the 
mercurials, in many cases, are followed by a 
cure of the disease, it has not always been fol- 
lowed by success. Not only has it shown fail- 
ures but in addition, much time has been re- 



314 THE HYPODERMIC SYRINGE 

quired to obtain permanent results through 
the use of the mercurials. As a rule not less 
than two years have been required to eradicate 
the disease under the use of mercury. 

Arsenic has been known to be an antidote 
against syphilis for upwards of a century, as 
in 1810 G. N. Hill mentioned it in cases where 
mercury failed. However, it has only been 
within the past decade or two that it has been 
employed to any great extent, this probably 
being due partly to the fact that none of the 
known arsenicals gave the desired results with- 
out undesirable drug effects. Sodium cacody- 
late was the first arsenical compound to give 
anything like the desired results but it was not 
demonstrated that it invariably brought about 
a cure in all cases. Still later and within the 
past decade, Ehrlich introduced arsenobenzol, 
or what is better known "salvarsan," which 
gave phenominal results in case after case. 
Despite these results, arsenobenzol, as time 
went on, was shown not to be invariably suc- 
cessful in the eradication of the disease and 
today we find this drug, combined with mer- 
cury, employed in the majority of cases. Sal- 
varsan, as originally manufactured, required 
the services of a chemist whenever an injection 
of the drug was to be given as the placing of it 
in solution properly was such as to need a con- 
siderable technique. To overcome this, Ehr- 
lich offered a more readily soluble salt, neosal- 
varsan ; one requiring practically no assistance 
upon the part of the chemist and it is this 



THE HYPODERMIC SYRINGE 315 

latter product which is in many instances, the 
more popular today. 

The arsenic element of both salvarsan and 
sodium cacodylate is that which is the spirlli- 
cide and in so far as drug poisoning is con- 
cerned, it is contended that arsenobenzol pre- 
sents no greater danger than do the mercurials. 
Wechselmann reports 4500 injections without a 
single case showing drug intoxication. 

Atoxyl (sodium-amine-phenyl-arsenate) is 
another arsenic compound which is also em- 
ployed, as is mercury cacodylate (mercury di- 
methyl arsenate), and in certain selected cases, 
in which there is anemia, iron cacodylate (iron 
di-methyl arsenate). None of these show drug 
intoxication if employed in proper dosage and 
under proper indications. 

Among the mercurials which are employed 
are those already mentioned and in addition 
mercury benzoate, 1 c.c. of the solution of the 
salt in water representing % grain of mercury 
as metal; mercury sozo-iodolate, 1 c.c. of a 
watery solution being equal to 1-12 grain of 
metallic mercury ; mercury salicylate ; gray oil, 
an emulsion of metallic mercury in an oil jelly 
and containing 1 grain of the metal per % c.c. ; 
mercury succinimide; mercury bichloride; as 
well as other of the soluble forms of salts of 
the metal as mentioned under the chapter de- 
voted to mercurials. 

With the introduction of the Wasserman 
test reaction in the diagnosis of syphilis, much 
of the guess-work, incident to treatment and 



316 THE HYPODERMIC SYRINGE 

other matters connected with the disease, has 
been eradicated and today we are reasonably 
sure, in the absence of this reaction, that our 
patient is free therefrom. Bearing in mind that 
the arsenic compounds are not invariably cura- 
tive, it is necessary that a course of mercurial 
treatment be adopted in practically all cases 
and continued until such time as the Wasser- 
mann has been negative for a sufficient time to 
warrant the knowledge of an absolute cure. In 
this connection it is suggested that the salicyl- 
ate of mercury is the best salt to employ, al- 
though some favor the succinimide. 

It will not be necessary to go into details as 
to the preparation and use of any of the drugs 
mentioned as the technique has been so thor- 
oughly discussed elsewhere as to hardly war- 
rant repetition. It goes without saying that all 
the different agents should be in such shape 
as to be readily absorbed. Primarily, as was 
the case with atoxyl and sodium cacodylate, 
salvarsan was injected intramuscularly but to- 
day we find the intravenous application be- 
coming of greater popularity. Some author- 
ities suggest that a dose of from 0.4 to 0.5 
grams of salvarsan be administered intraven- 
ously to be followed in 48 hours by an intra- 
muscular injection of from 0.3 to 0.4 grams. 
This should invariably, no matter which meth- 
od is employed, be followed by regular injec- 
tions of small doses of mercury salicylate, into 
the lumbar muscles. 



THE HYPODERMIC SYRINGE 317 

As to the technic, there is but little variance 
from other hypodermic or intravenous injec- 
tions. Every antiseptic precaution should be 
taken, and more especially when the intra- 
venous method is followed. In the latter meth- 
od some favor the use of the syringe, while 
others prefer the introduction of the drug by 
gravity. The latter is possibly the better way 
in that undue force is not expended in throw- 
ing the solution into the vein, as might possibly 
be the case through use of the syringe. The 
buttock is the usual site of intramuscular in- 
jections and these should be thrown deeply into 
the tissues. The intravenous method offers the 
advantage of quicker and more thorough ab- 
sorption of the drug and is undoubtedly the 
better procedure. 

It is possible, as time goes on, that we will 
be offered a serum or bacterial vaccine for the 
treatment of syphilis but thus far none worthy 
of mention has been offered. 



